chr14-75578617-G-C

Position:

• chr14-75578617-G-C

Variant summary

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

The ENST00000455232.1(FLVCR2-AS1):​n.972C>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0685 in 360,156 control chromosomes in the GnomAD database, including 2,972 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.11 (2329 hom., cov: 31)
  • Exomes 𝑓: 0.038 (643 hom.)
• Consequence: FLVCR2-AS1 ENST00000455232.1 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -2.42

Genes affected

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

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 14-75578617-G-C is Benign according to our data. Variant chr14-75578617-G-C is described in ClinVar as [Benign]. Clinvar id is 314403.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.306 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FLVCR2-AS1	NR_110552.1	n.972C>G		non_coding_transcript_exon_variant	1/3
FLVCR2	NM_017791.3	c.-356G>C		upstream_gene_variant		ENST00000238667.9	NP_060261.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FLVCR2-AS1	ENST00000455232.1	n.972C>G		non_coding_transcript_exon_variant	1/3	1
FLVCR2-AS1	ENST00000693551.1	n.1036C>G		non_coding_transcript_exon_variant	1/1
FLVCR2	ENST00000238667.9	c.-356G>C		upstream_gene_variant		1	NM_017791.3	ENSP00000238667.4

Frequencies

GnomAD3 genomes AF: 0.110 AC: 16684 AN: 151390 Hom.: 2315 Cov.: 31

Gnomad AFR AF: 0.310

Gnomad AMI AF: 0.0340

Gnomad AMR AF: 0.128

Gnomad ASJ AF: 0.0222

Gnomad EAS AF: 0.224

Gnomad SAS AF: 0.0626

Gnomad FIN AF: 0.0108

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.00300

Gnomad OTH AF: 0.0896

GnomAD4 exome AF: 0.0379 AC: 7901 AN: 208648 Hom.: 643 Cov.: 0 AF XY: 0.0395 AC XY: 4437 AN XY: 112448

Gnomad4 AFR exome AF: 0.308

Gnomad4 AMR exome AF: 0.140

Gnomad4 ASJ exome AF: 0.0198

Gnomad4 EAS exome AF: 0.219

Gnomad4 SAS exome AF: 0.0563

Gnomad4 FIN exome AF: 0.0101

Gnomad4 NFE exome AF: 0.00233

Gnomad4 OTH exome AF: 0.0334

GnomAD4 genome AF: 0.111 AC: 16754 AN: 151508 Hom.: 2329 Cov.: 31 AF XY: 0.111 AC XY: 8241 AN XY: 74080

Gnomad4 AFR AF: 0.311

Gnomad4 AMR AF: 0.129

Gnomad4 ASJ AF: 0.0222

Gnomad4 EAS AF: 0.224

Gnomad4 SAS AF: 0.0621

Gnomad4 FIN AF: 0.0108

Gnomad4 NFE AF: 0.00300

Gnomad4 OTH AF: 0.0911

Alfa AF: 0.00473 Hom.: 3

Bravo AF: 0.136

Asia WGS AF: 0.130 AC: 451 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

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	Oct 28, 2019	- -

Fowler syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.093
DANN	Benign	0.47

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: rs3813550; hg19: chr14-76044960;