chr14-75579019-T-C

Position:

chr14-75579019-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_017791.3(FLVCR2):c.47T>C(p.Val16Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.268 in 1,613,644 control chromosomes in the GnomAD database, including 69,852 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.37 ( 13615 hom., cov: 31)

Exomes 𝑓: 0.26 ( 56237 hom. )

Consequence

FLVCR2
NM_017791.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.852

Variant links:

Genes affected

FLVCR2 (HGNC:20105): (FLVCR choline and putative heme transporter 2) This gene encodes a member of the major facilitator superfamily. The encoded transmembrane protein is a calcium transporter. Unlike the related protein feline leukemia virus subgroup C receptor 1, the protein encoded by this locus does not bind to feline leukemia virus subgroup C envelope protein. The encoded protein may play a role in development of brain vascular endothelial cells, as mutations at this locus have been associated with proliferative vasculopathy and hydranencephaly-hydrocephaly syndrome. Alternatively spliced transcript variants have been described.[provided by RefSeq, Aug 2010]

FLVCR2 links:

FLVCR2-AS1 (HGNC:55854): (FLVCR2 antisense RNA 1)

FLVCR2-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=3.4904954E-6).

BP6

Variant 14-75579019-T-C is Benign according to our data. Variant chr14-75579019-T-C is described in ClinVar as [Benign]. Clinvar id is 95818.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.658 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FLVCR2	NM_017791.3 link	c.47T>C	p.Val16Ala	missense_variant	1/10	ENST00000238667.9	NP_060261.2	Q9UPI3-1
FLVCR2-AS1	NR_110552.1 link	n.570A>G		non_coding_transcript_exon_variant	1/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
FLVCR2	ENST00000238667.9 link	c.47T>C	p.Val16Ala	missense_variant	1/10	1	NM_017791.3	ENSP00000238667.4	Q9UPI3-1
FLVCR2-AS1	ENST00000455232.1 link	n.570A>G		non_coding_transcript_exon_variant	1/3	1
FLVCR2-AS1	ENST00000693551.1 link	n.634A>G		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes

AF:

0.374

AC:

56753

AN:

151716

Hom.:

13577

Cov.:

show subpopulations

Gnomad AFR

AF:

0.664

Gnomad AMI

AF:

0.357

Gnomad AMR

AF:

0.328

Gnomad ASJ

AF:

0.281

Gnomad EAS

AF:

0.556

Gnomad SAS

AF:

0.395

Gnomad FIN

AF:

0.229

Gnomad MID

AF:

0.264

Gnomad NFE

AF:

0.222

Gnomad OTH

AF:

0.354

GnomAD3 exomes

AF:

0.322

AC:

81012

AN:

251410

Hom.:

15588

AF XY:

0.313

AC XY:

42580

AN XY:

135908

show subpopulations

Gnomad AFR exome

AF:

0.676

Gnomad AMR exome

AF:

0.369

Gnomad ASJ exome

AF:

0.277

Gnomad EAS exome

AF:

0.573

Gnomad SAS exome

AF:

0.394

Gnomad FIN exome

AF:

0.235

Gnomad NFE exome

AF:

0.220

Gnomad OTH exome

AF:

0.280

GnomAD4 exome

AF:

0.257

AC:

375928

AN:

1461810

Hom.:

56237

Cov.:

AF XY:

0.259

AC XY:

188451

AN XY:

727202

show subpopulations

Gnomad4 AFR exome

AF:

0.687

Gnomad4 AMR exome

AF:

0.364

Gnomad4 ASJ exome

AF:

0.277

Gnomad4 EAS exome

AF:

0.575

Gnomad4 SAS exome

AF:

0.390

Gnomad4 FIN exome

AF:

0.236

Gnomad4 NFE exome

AF:

0.217

Gnomad4 OTH exome

AF:

0.287

GnomAD4 genome

AF:

0.374

AC:

56851

AN:

151834

Hom.:

13615

Cov.:

AF XY:

0.374

AC XY:

27757

AN XY:

74194

show subpopulations

Gnomad4 AFR

AF:

0.665

Gnomad4 AMR

AF:

0.328

Gnomad4 ASJ

AF:

0.281

Gnomad4 EAS

AF:

0.555

Gnomad4 SAS

AF:

0.395

Gnomad4 FIN

AF:

0.229

Gnomad4 NFE

AF:

0.222

Gnomad4 OTH

AF:

0.357

Alfa

AF:

0.259

Hom.:

14574

Bravo

AF:

0.399

TwinsUK

AF:

0.217

AC:

804

ALSPAC

AF:

0.212

AC:

817

ESP6500AA

AF:

0.663

AC:

2920

ESP6500EA

AF:

0.225

AC:

1931

ExAC

AF:

0.325

AC:

39478

Asia WGS

AF:

0.431

AC:

1500

AN:

3478

EpiCase

AF:

0.224

EpiControl

AF:

0.228

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 11, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Eurofins Ntd Llc (ga)

Jul 03, 2013

- -

Posterior column ataxia-retinitis pigmentosa syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Fowler syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.059

BayesDel_addAF

Benign

-0.79

BayesDel_noAF

Benign

-0.77

CADD

Benign

5.7

DANN

Benign

0.34

DEOGEN2

Benign

0.0089

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.0022

LIST_S2

Benign

0.12

MetaRNN

Benign

0.0000035

MetaSVM

Benign

-0.96

MutationAssessor

Benign

-0.69

PrimateAI

Benign

0.29

PROVEAN

Benign

0.45

REVEL

Benign

0.0060

Sift

Benign

1.0

Sift4G

Benign

0.58

Polyphen

0.0

Vest4

0.012

MPC

0.32

ClinPred

0.000011

GERP RS

-2.6

Varity_R

0.021

gMVP

0.16

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