14-75578850-GTC-G

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_017791.3(FLVCR2):c.-119_-118del variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.169 in 901,688 control chromosomes in the GnomAD database, including 13,607 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.18 (2581 hom., cov: 28)
  • Exomes 𝑓: 0.17 (11026 hom.)
• Consequence: FLVCR2 NM_017791.3 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.105

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 -16 ACMG points.

• BP6: Variant 14-75578850-GTC-G is Benign according to our data. Variant chr14-75578850-GTC-G is described in ClinVar as [Benign]. Clinvar id is 314404.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.214 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FLVCR2	NM_017791.3	c.-119_-118del		5_prime_UTR_variant	1/10	ENST00000238667.9
FLVCR2-AS1	NR_110552.1	n.737_738del		non_coding_transcript_exon_variant	1/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FLVCR2	ENST00000238667.9	c.-119_-118del		5_prime_UTR_variant	1/10	1	NM_017791.3	P1
FLVCR2-AS1	ENST00000455232.1	n.737_738del		non_coding_transcript_exon_variant	1/3	1
FLVCR2-AS1	ENST00000693551.1	n.801_802del		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.178 AC: 27051 AN: 151962 Hom.: 2584 Cov.: 28

Gnomad AFR AF: 0.218

Gnomad AMI AF: 0.107

Gnomad AMR AF: 0.188

Gnomad ASJ AF: 0.194

Gnomad EAS AF: 0.0847

Gnomad SAS AF: 0.223

Gnomad FIN AF: 0.137

Gnomad MID AF: 0.217

Gnomad NFE AF: 0.162

Gnomad OTH AF: 0.183

GnomAD4 exome AF: 0.167 AC: 124938 AN: 749608 Hom.: 11026 AF XY: 0.170 AC XY: 66961 AN XY: 394224

Gnomad4 AFR exome AF: 0.216

Gnomad4 AMR exome AF: 0.173

Gnomad4 ASJ exome AF: 0.196

Gnomad4 EAS exome AF: 0.0804

Gnomad4 SAS exome AF: 0.221

Gnomad4 FIN exome AF: 0.145

Gnomad4 NFE exome AF: 0.163

Gnomad4 OTH exome AF: 0.167

GnomAD4 genome AF: 0.178 AC: 27069 AN: 152080 Hom.: 2581 Cov.: 28 AF XY: 0.178 AC XY: 13216 AN XY: 74358

Gnomad4 AFR AF: 0.218

Gnomad4 AMR AF: 0.188

Gnomad4 ASJ AF: 0.194

Gnomad4 EAS AF: 0.0849

Gnomad4 SAS AF: 0.222

Gnomad4 FIN AF: 0.137

Gnomad4 NFE AF: 0.162

Gnomad4 OTH AF: 0.184

Alfa AF: 0.165 Hom.: 276

Bravo AF: 0.178

Asia WGS AF: 0.177 AC: 619 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 26, 2021

- -

Fowler syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs1322268460; hg19: chr14-76045193;