NM_014053.4:c.1631C>T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_014053.4(FLVCR1):c.1631C>T(p.Thr544Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.467 in 1,609,178 control chromosomes in the GnomAD database, including 180,923 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T544I) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.40 ( 13343 hom., cov: 31)

Exomes 𝑓: 0.47 ( 167580 hom. )

Consequence

FLVCR1
NM_014053.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: -0.572

Publications

56 publications found

Variant links:

Genes affected

FLVCR1 (HGNC:24682): (FLVCR choline and heme transporter 1) This gene encodes a member of the major facilitator superfamily of transporter proteins. The encoded protein is a heme transporter that may play a critical role in erythropoiesis by protecting developing erythroid cells from heme toxicity. This gene may play a role in posterior column ataxia with retinitis pigmentosa and the hematological disorder Diamond-Blackfan syndrome. [provided by RefSeq, Jan 2011]

FLVCR1 Gene-Disease associations (from GenCC):

FLVCR1-related retinopathy with or without ataxia
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
posterior column ataxia-retinitis pigmentosa syndrome
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Orphanet, Illumina

FLVCR1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=2.3459066E-5).

BP6

Variant 1-212895253-C-T is Benign according to our data. Variant chr1-212895253-C-T is described in ClinVar as Benign. ClinVar VariationId is 129103.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.503 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014053.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FLVCR1	NM_014053.4	MANE Select	c.1631C>T	p.Thr544Met	missense	Exon 10 of 10	NP_054772.1	Q9Y5Y0-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FLVCR1	ENST00000366971.9	TSL:1 MANE Select	c.1631C>T	p.Thr544Met	missense	Exon 10 of 10	ENSP00000355938.4	Q9Y5Y0-1
FLVCR1	ENST00000867613.1		c.1721C>T	p.Thr574Met	missense	Exon 11 of 11	ENSP00000537672.1
FLVCR1	ENST00000971333.1		c.1658C>T	p.Thr553Met	missense	Exon 10 of 10	ENSP00000641392.1

Frequencies

GnomAD3 genomes

AF:

0.395

AC:

59958

AN:

151630

Hom.:

13346

Cov.:

show subpopulations

Gnomad AFR

AF:

0.196

Gnomad AMI

AF:

0.399

Gnomad AMR

AF:

0.329

Gnomad ASJ

AF:

0.377

Gnomad EAS

AF:

0.475

Gnomad SAS

AF:

0.520

Gnomad FIN

AF:

0.574

Gnomad MID

AF:

0.408

Gnomad NFE

AF:

0.490

Gnomad OTH

AF:

0.391

GnomAD2 exomes

AF:

0.443

AC:

111417

AN:

251248

AF XY:

0.457

show subpopulations

Gnomad AFR exome

AF:

0.190

Gnomad AMR exome

AF:

0.283

Gnomad ASJ exome

AF:

0.375

Gnomad EAS exome

AF:

0.478

Gnomad FIN exome

AF:

0.571

Gnomad NFE exome

AF:

0.491

Gnomad OTH exome

AF:

0.433

GnomAD4 exome

AF:

0.474

AC:

690842

AN:

1457430

Hom.:

167580

Cov.:

AF XY:

0.476

AC XY:

344913

AN XY:

725308

show subpopulations

African (AFR)

AF:

0.184

AC:

6152

AN:

33428

American (AMR)

AF:

0.289

AC:

12924

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.377

AC:

9847

AN:

26112

East Asian (EAS)

AF:

0.474

AC:

18775

AN:

39630

South Asian (SAS)

AF:

0.500

AC:

43111

AN:

86158

European-Finnish (FIN)

AF:

0.567

AC:

30287

AN:

53418

Middle Eastern (MID)

AF:

0.446

AC:

2570

AN:

5764

European-Non Finnish (NFE)

AF:

0.488

AC:

540364

AN:

1107982

Other (OTH)

AF:

0.445

AC:

26812

AN:

60222

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.456

Heterozygous variant carriers

16853

33705

50558

67410

84263

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

15724

31448

47172

62896

78620

<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:

0.395

AC:

59953

AN:

151748

Hom.:

13343

Cov.:

AF XY:

0.401

AC XY:

29714

AN XY:

74114

show subpopulations

African (AFR)

AF:

0.196

AC:

8097

AN:

41354

American (AMR)

AF:

0.328

AC:

5001

AN:

15234

Ashkenazi Jewish (ASJ)

AF:

0.377

AC:

1306

AN:

3468

East Asian (EAS)

AF:

0.476

AC:

2450

AN:

5150

South Asian (SAS)

AF:

0.520

AC:

2497

AN:

4804

European-Finnish (FIN)

AF:

0.574

AC:

6012

AN:

10468

Middle Eastern (MID)

AF:

0.405

AC:

119

AN:

294

European-Non Finnish (NFE)

AF:

0.490

AC:

33288

AN:

67952

Other (OTH)

AF:

0.388

AC:

819

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1698

3397

5095

6794

8492

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

584

1168

1752

2336

2920

<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:

0.456

Hom.:

73792

Bravo

AF:

0.363

TwinsUK

AF:

0.496

AC:

1839

ALSPAC

AF:

0.492

AC:

1898

ESP6500AA

AF:

0.209

AC:

920

ESP6500EA

AF:

0.475

AC:

4086

ExAC

AF:

0.449

AC:

54534

Asia WGS

AF:

0.452

AC:

1573

AN:

3478

EpiCase

AF:

0.475

EpiControl

AF:

0.472

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Posterior column ataxia-retinitis pigmentosa syndrome (4)

not provided (3)

not specified (3)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.071

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.36

CADD

Benign

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.043

Eigen

Benign

-0.80

Eigen_PC

Benign

-0.98

FATHMM_MKL

Benign

0.019

LIST_S2

Benign

0.45

MetaRNN

Benign

0.000023

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.9

PhyloP100

-0.57

PrimateAI

Benign

0.33

PROVEAN

Benign

-0.30

REVEL

Uncertain

0.32

Sift

Uncertain

0.0070

Sift4G

Uncertain

0.042

Polyphen

0.86

Vest4

0.036

MPC

0.30

ClinPred

0.0033

GERP RS

-2.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.014

gMVP

0.41

Mutation Taster

=99/1

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over