chr19-48965830-T-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000146.4(FTL):c.163T>C(p.Leu55Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.523 in 1,613,848 control chromosomes in the GnomAD database, including 222,359 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.51 ( 19872 hom., cov: 33)

Exomes 𝑓: 0.52 ( 202487 hom. )

Consequence

FTL
NM_000146.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts P:1B:19

Conservation

PhyloP100: -0.251

Publications

41 publications found

Variant links:

Genes affected

FTL (HGNC:3999): (ferritin light chain) This gene encodes the light subunit of the ferritin protein. Ferritin is the major intracellular iron storage protein in prokaryotes and eukaryotes. It is composed of 24 subunits of the heavy and light ferritin chains. Variation in ferritin subunit composition may affect the rates of iron uptake and release in different tissues. A major function of ferritin is the storage of iron in a soluble and nontoxic state. Defects in this light chain ferritin gene are associated with several neurodegenerative diseases and hyperferritinemia-cataract syndrome. This gene has multiple pseudogenes. [provided by RefSeq, Jul 2008]

FTL Gene-Disease associations (from GenCC):

hereditary hyperferritinemia with congenital cataracts
Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Genomics England PanelApp, Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae), Orphanet
neuroferritinopathy
Inheritance: AD Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Orphanet
L-ferritin deficiency
Inheritance: Unknown, AD Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Orphanet
genetic hyperferritinemia without iron overload
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

FTL links:

ENSG00000305635 (HGNC:):

ENSG00000305635 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.69).

BP6

Variant 19-48965830-T-C is Benign according to our data. Variant chr19-48965830-T-C is described in ClinVar as Benign. ClinVar VariationId is 156440.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.251 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.538 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FTL	NM_000146.4 link	c.163T>C	p.Leu55Leu	synonymous_variant	Exon 2 of 4	ENST00000331825.11	NP_000137.2	P02792A0A384MDR3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FTL	ENST00000331825.11 link	c.163T>C	p.Leu55Leu	synonymous_variant	Exon 2 of 4	1	NM_000146.4	ENSP00000366525.2		P02792

Frequencies

GnomAD3 genomes

AF:

0.509

AC:

77408

AN:

151996

Hom.:

19855

Cov.:

show subpopulations

Gnomad AFR

AF:

0.482

Gnomad AMI

AF:

0.590

Gnomad AMR

AF:

0.522

Gnomad ASJ

AF:

0.569

Gnomad EAS

AF:

0.426

Gnomad SAS

AF:

0.382

Gnomad FIN

AF:

0.446

Gnomad MID

AF:

0.570

Gnomad NFE

AF:

0.543

Gnomad OTH

AF:

0.540

GnomAD2 exomes

AF:

0.501

AC:

125886

AN:

251284

AF XY:

0.499

show subpopulations

Gnomad AFR exome

AF:

0.479

Gnomad AMR exome

AF:

0.526

Gnomad ASJ exome

AF:

0.570

Gnomad EAS exome

AF:

0.425

Gnomad FIN exome

AF:

0.440

Gnomad NFE exome

AF:

0.541

Gnomad OTH exome

AF:

0.520

GnomAD4 exome

AF:

0.524

AC:

765999

AN:

1461732

Hom.:

202487

Cov.:

AF XY:

0.521

AC XY:

379096

AN XY:

727186

show subpopulations

African (AFR)

AF:

0.486

AC:

16270

AN:

33480

American (AMR)

AF:

0.525

AC:

23460

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.574

AC:

15012

AN:

26136

East Asian (EAS)

AF:

0.423

AC:

16785

AN:

39700

South Asian (SAS)

AF:

0.397

AC:

34258

AN:

86252

European-Finnish (FIN)

AF:

0.443

AC:

23643

AN:

53370

Middle Eastern (MID)

AF:

0.563

AC:

3246

AN:

5766

European-Non Finnish (NFE)

AF:

0.541

AC:

601971

AN:

1111918

Other (OTH)

AF:

0.519

AC:

31354

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

23027

46054

69081

92108

115135

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

16914

33828

50742

67656

84570

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.509

AC:

77466

AN:

152116

Hom.:

19872

Cov.:

AF XY:

0.503

AC XY:

37402

AN XY:

74348

show subpopulations

African (AFR)

AF:

0.482

AC:

20016

AN:

41488

American (AMR)

AF:

0.521

AC:

7964

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.569

AC:

1977

AN:

3472

East Asian (EAS)

AF:

0.425

AC:

2197

AN:

5164

South Asian (SAS)

AF:

0.383

AC:

1846

AN:

4824

European-Finnish (FIN)

AF:

0.446

AC:

4725

AN:

10592

Middle Eastern (MID)

AF:

0.575

AC:

169

AN:

294

European-Non Finnish (NFE)

AF:

0.543

AC:

36885

AN:

67984

Other (OTH)

AF:

0.545

AC:

1150

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1995

3990

5986

7981

9976

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

690

1380

2070

2760

3450

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.536

Hom.:

9374

Bravo

AF:

0.517

Asia WGS

AF:

0.390

AC:

1357

AN:

3478

EpiCase

AF:

0.556

EpiControl

AF:

0.562

ClinVar

Significance: Benign

Submissions summary: Pathogenic:1Benign:19

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:8

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Genome Diagnostics Laboratory, Amsterdam University Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Jul 31, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 74% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy, Progressive Myoclonus Epilepsy and Abnormal Movements and Neurodegeneration with brain iron accumulation. Number of patients: 69. Only high quality variants are reported. -

Aug 15, 2013

Genetic Services Laboratory, University of Chicago

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Hereditary hyperferritinemia with congenital cataracts

Benign:3

May 28, 2019

Mendelics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Aug 10, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Neuroferritinopathy

Benign:2

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Aug 10, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Mar 24, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

sporadic abdominal aortic aneurysm

Pathogenic:1

Sep 21, 2014

TilsonLab, Columbia University

Significance:Likely pathogenic

Review Status:no assertion criteria provided

Collection Method:research

Observed frequency is 15/19 = 0.789 patients with abdominal aortic aneurysm versus heterozygosity is described in "Variation Viewer" as 0.496. -

Hereditary hyperferritinemia with congenital cataracts;C1853578:Neuroferritinopathy

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Glycogen storage disease due to muscle and heart glycogen synthase deficiency

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

L-ferritin deficiency

Benign:1

Aug 10, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Hereditary hyperferritinemia with congenital cataracts;C1853578:Neuroferritinopathy;C3810090:L-ferritin deficiency

Benign:1

Apr 17, 2023

Department of Pathology and Laboratory Medicine, Sinai Health System

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:research

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.69

CADD

Benign

(source)

DANN

Benign

0.79

PhyloP100

-0.25

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over