14-75604938-G-C

Position:

• chr14-75604938-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000238667.9(FLVCR2):​c.670-17141G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.195 in 152,102 control chromosomes in the GnomAD database, including 3,318 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.20 (3318 hom., cov: 32)
• Consequence: FLVCR2 ENST00000238667.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.44

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.551 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FLVCR2	NM_017791.3	c.670-17141G>C		intron_variant		ENST00000238667.9	NP_060261.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FLVCR2	ENST00000238667.9	c.670-17141G>C		intron_variant		1	NM_017791.3	ENSP00000238667	P1
FLVCR2	ENST00000554496.1	n.186+25297G>C		intron_variant, non_coding_transcript_variant		3
FLVCR2	ENST00000555385.1	n.58+25297G>C		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.195 AC: 29643 AN: 151984 Hom.: 3310 Cov.: 32

Gnomad AFR AF: 0.198

Gnomad AMI AF: 0.248

Gnomad AMR AF: 0.211

Gnomad ASJ AF: 0.183

Gnomad EAS AF: 0.568

Gnomad SAS AF: 0.265

Gnomad FIN AF: 0.157

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.163

Gnomad OTH AF: 0.189

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.195 AC: 29680 AN: 152102 Hom.: 3318 Cov.: 32 AF XY: 0.197 AC XY: 14663 AN XY: 74342

Gnomad4 AFR AF: 0.198

Gnomad4 AMR AF: 0.212

Gnomad4 ASJ AF: 0.183

Gnomad4 EAS AF: 0.568

Gnomad4 SAS AF: 0.265

Gnomad4 FIN AF: 0.157

Gnomad4 NFE AF: 0.163

Gnomad4 OTH AF: 0.193

Alfa AF: 0.0807 Hom.: 103

Bravo AF: 0.201

Asia WGS AF: 0.334 AC: 1165 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.48
DANN	Benign	0.58

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: rs10483871; hg19: chr14-76071281;