Variant 14-75578902-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_017791.3(FLVCR2):c.-71C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0333 in 1,387,586 control chromosomes in the GnomAD database, including 4,206 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.085 ( 1276 hom., cov: 32)

Exomes 𝑓: 0.027 ( 2930 hom. )

Consequence

FLVCR2
NM_017791.3 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.30

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 (BayesDel_noAF=-0.89).

BP6

Variant 14-75578902-C-T is Benign according to our data. Variant chr14-75578902-C-T is described in ClinVar as [Benign]. Clinvar id is 314407.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.221 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FLVCR2	NM_017791.3 link	c.-71C>T		5_prime_UTR_variant	1/10	ENST00000238667.9	NP_060261.2	Q9UPI3-1
FLVCR2-AS1	NR_110552.1 link	n.687G>A		non_coding_transcript_exon_variant	1/3

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	UniProt
FLVCR2	ENST00000238667 link	c.-71C>T	5_prime_UTR_variant	1/10	1	NM_017791.3	ENSP00000238667.4	Q9UPI3-1
FLVCR2-AS1	ENST00000455232.1 link	n.687G>A	non_coding_transcript_exon_variant	1/3	1
FLVCR2-AS1	ENST00000693551.1 link	n.751G>A	non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes

AF:

0.0844

AC:

12842

AN:

152122

Hom.:

1270

Cov.:

show subpopulations

Gnomad AFR

AF:

0.214

Gnomad AMI

AF:

0.0340

Gnomad AMR

AF:

0.123

Gnomad ASJ

AF:

0.0222

Gnomad EAS

AF:

0.232

Gnomad SAS

AF:

0.0627

Gnomad FIN

AF:

0.0113

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.00304

Gnomad OTH

AF:

0.0714

GnomAD4 exome

AF:

0.0270

AC:

33342

AN:

1235346

Hom.:

2930

Cov.:

AF XY:

0.0264

AC XY:

16518

AN XY:

625062

show subpopulations

Gnomad4 AFR exome

AF:

0.219

Gnomad4 AMR exome

AF:

0.177

Gnomad4 ASJ exome

AF:

0.0223

Gnomad4 EAS exome

AF:

0.245

Gnomad4 SAS exome

AF:

0.0591

Gnomad4 FIN exome

AF:

0.0123

Gnomad4 NFE exome

AF:

0.00210

Gnomad4 OTH exome

AF:

0.0360

GnomAD4 genome

AF:

0.0847

AC:

12892

AN:

152240

Hom.:

1276

Cov.:

AF XY:

0.0873

AC XY:

6499

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.215

Gnomad4 AMR

AF:

0.123

Gnomad4 ASJ

AF:

0.0222

Gnomad4 EAS

AF:

0.232

Gnomad4 SAS

AF:

0.0623

Gnomad4 FIN

AF:

0.0113

Gnomad4 NFE

AF:

0.00304

Gnomad4 OTH

AF:

0.0731

Alfa

AF:

0.0336

Hom.:

Bravo

AF:

0.104

Asia WGS

AF:

0.122

AC:

422

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 23, 2019	- -

Posterior column ataxia-retinitis pigmentosa syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.81

DANN

Benign

0.67

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