rs2230267

Variant names:

Variant summary

Our verdict is Benign. Variant got -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:18

Conservation

PhyloP100: -0.251

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 156440.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-48965830-T-C is described in Lovd as [Benign]. Variant chr19-48965830-T-C is described in Lovd as [Likely_benign].

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

GnomAD3 exomes

AF:

0.501

AC:

125886

AN:

251284

Hom.:

32088

AF XY:

0.499

AC XY:

67846

AN XY:

135854

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 SAS exome

AF:

0.396

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

Gnomad4 AFR exome

AF:

0.486

Gnomad4 AMR exome

AF:

0.525

Gnomad4 ASJ exome

AF:

0.574

Gnomad4 EAS exome

AF:

0.423

Gnomad4 SAS exome

AF:

0.397

Gnomad4 FIN exome

AF:

0.443

Gnomad4 NFE exome

AF:

0.541

Gnomad4 OTH exome

AF:

0.519

GnomAD4 genome

AF:

0.509

AC:

77466

AN:

152116

Hom.:

19872

Cov.:

AF XY:

0.503

AC XY:

37402

AN XY:

74348

show subpopulations

Gnomad4 AFR

AF:

0.482

Gnomad4 AMR

AF:

0.521

Gnomad4 ASJ

AF:

0.569

Gnomad4 EAS

AF:

0.425

Gnomad4 SAS

AF:

0.383

Gnomad4 FIN

AF:

0.446

Gnomad4 NFE

AF:

0.543

Gnomad4 OTH

AF:

0.545

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:18

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:8

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

- -

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. -

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Aug 15, 2013

Genetic Services Laboratory, University of Chicago

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Genome Diagnostics Laboratory, Amsterdam University Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

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

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

- -

Hereditary hyperferritinemia with congenital cataracts

Benign:3

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

- -

May 28, 2019

Mendelics

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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.69

CADD

Benign

DANN

Benign

0.79

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over