14-75578902-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.30

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

ACMG classification

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	UniProt
FLVCR2	NM_017791.3	c.-71C>T		5_prime_UTR_variant	1/10	ENST00000238667.9
FLVCR2-AS1	NR_110552.1	n.687G>A		non_coding_transcript_exon_variant	1/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FLVCR2	ENST00000238667.9	c.-71C>T		5_prime_UTR_variant	1/10	1	NM_017791.3	P1
FLVCR2-AS1	ENST00000455232.1	n.687G>A		non_coding_transcript_exon_variant	1/3	1
FLVCR2-AS1	ENST00000693551.1	n.751G>A		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.0844 AC: 12842 AN: 152122 Hom.: 1270 Cov.: 32

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.: 17 AF XY: 0.0264 AC XY: 16518 AN XY: 625062

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.: 32 AF XY: 0.0873 AC XY: 6499 AN XY: 74450

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.: 84

Bravo AF: 0.104

Asia WGS AF: 0.122 AC: 422 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

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 23, 2019

- -

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

Other links and lift over

dbSNP: rs11849590; hg19: chr14-76045245;