rs2321743

Positions:

• chr3-157290807-G-A

Variant summary

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

The NM_001167912.2(VEPH1):​c.2011-4133C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.452 in 151,940 control chromosomes in the GnomAD database, including 16,404 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 0.45 (16404 hom., cov: 32)
• Consequence: VEPH1 NM_001167912.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.309

Genes affected

VEPH1 (HGNC:25735): (ventricular zone expressed PH domain containing 1) Predicted to enable phosphatidylinositol-5-phosphate binding activity. Involved in negative regulation of SMAD protein signal transduction and negative regulation of transforming growth factor beta receptor signaling pathway. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.583 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VEPH1	NM_001167912.2	c.2011-4133C>T		intron_variant		ENST00000362010.7
LOC101928236	XR_007096141.1	n.3208+4466G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VEPH1	ENST00000362010.7	c.2011-4133C>T		intron_variant		1	NM_001167912.2	P1
	ENST00000487238.5	n.331+51008G>A		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.452 AC: 68615 AN: 151822 Hom.: 16391 Cov.: 32

Gnomad AFR AF: 0.304

Gnomad AMI AF: 0.651

Gnomad AMR AF: 0.593

Gnomad ASJ AF: 0.450

Gnomad EAS AF: 0.422

Gnomad SAS AF: 0.348

Gnomad FIN AF: 0.434

Gnomad MID AF: 0.341

Gnomad NFE AF: 0.520

Gnomad OTH AF: 0.462

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

GnomAD4 genome AF: 0.452 AC: 68659 AN: 151940 Hom.: 16404 Cov.: 32 AF XY: 0.448 AC XY: 33294 AN XY: 74272

Gnomad4 AFR AF: 0.304

Gnomad4 AMR AF: 0.593

Gnomad4 ASJ AF: 0.450

Gnomad4 EAS AF: 0.422

Gnomad4 SAS AF: 0.347

Gnomad4 FIN AF: 0.434

Gnomad4 NFE AF: 0.520

Gnomad4 OTH AF: 0.466

Alfa AF: 0.493 Hom.: 3240

Bravo AF: 0.459

Asia WGS AF: 0.392 AC: 1361 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	4.7
DANN	Benign	0.35

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: rs2321743; hg19: chr3-157008596;