Variant 14-75578877-T-C 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.-96T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.26 in 1,135,086 control chromosomes in the GnomAD database, including 48,224 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.36 ( 12980 hom., cov: 32)

Exomes 𝑓: 0.24 ( 35244 hom. )

Consequence

FLVCR2
NM_017791.3 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.440

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:

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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 14-75578877-T-C is Benign according to our data. Variant chr14-75578877-T-C is described in ClinVar as [Benign]. Clinvar id is 314406.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.654 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FLVCR2	NM_017791.3 linkuse as main transcript	c.-96T>C		5_prime_UTR_variant	1/10	ENST00000238667.9
FLVCR2-AS1	NR_110552.1 linkuse as main transcript	n.712A>G		non_coding_transcript_exon_variant	1/3

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FLVCR2	ENST00000238667.9 linkuse as main transcript	c.-96T>C	5_prime_UTR_variant	1/10	1	NM_017791.3	P1	Q9UPI3-1
FLVCR2-AS1	ENST00000455232.1 linkuse as main transcript	n.712A>G	non_coding_transcript_exon_variant	1/3	1
FLVCR2-AS1	ENST00000693551.1 linkuse as main transcript	n.776A>G	non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes

AF:

0.360

AC:

54685

AN:

151930

Hom.:

12945

Cov.:

show subpopulations

Gnomad AFR

AF:

0.660

Gnomad AMI

AF:

0.355

Gnomad AMR

AF:

0.320

Gnomad ASJ

AF:

0.278

Gnomad EAS

AF:

0.556

Gnomad SAS

AF:

0.309

Gnomad FIN

AF:

0.182

Gnomad MID

AF:

0.258

Gnomad NFE

AF:

0.208

Gnomad OTH

AF:

0.346

GnomAD4 exome

AF:

0.245

AC:

240566

AN:

983038

Hom.:

35244

Cov.:

AF XY:

0.244

AC XY:

123846

AN XY:

506874

show subpopulations

Gnomad4 AFR exome

AF:

0.673

Gnomad4 AMR exome

AF:

0.352

Gnomad4 ASJ exome

AF:

0.273

Gnomad4 EAS exome

AF:

0.571

Gnomad4 SAS exome

AF:

0.299

Gnomad4 FIN exome

AF:

0.195

Gnomad4 NFE exome

AF:

0.202

Gnomad4 OTH exome

AF:

0.272

GnomAD4 genome

AF:

0.360

AC:

54780

AN:

152048

Hom.:

12980

Cov.:

AF XY:

0.357

AC XY:

26555

AN XY:

74338

show subpopulations

Gnomad4 AFR

AF:

0.661

Gnomad4 AMR

AF:

0.321

Gnomad4 ASJ

AF:

0.278

Gnomad4 EAS

AF:

0.556

Gnomad4 SAS

AF:

0.308

Gnomad4 FIN

AF:

0.182

Gnomad4 NFE

AF:

0.208

Gnomad4 OTH

AF:

0.349

Alfa

AF:

0.267

Hom.:

1438

Bravo

AF:

0.390

Asia WGS

AF:

0.385

AC:

1338

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

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. -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 11, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

DANN

Benign

0.68

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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