3-157292297-T-C

Variant names:

• chr3-157292297-T-C
• rs1403105
• NM_001167912.2:c.2011-5623A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001167912.2(VEPH1):​c.2011-5623A>G 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 152,026 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: 31)
• Consequence: VEPH1 NM_001167912.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.392
• Publications: 5 publications found

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]

LINC00881 (HGNC:48567): (long intergenic non-protein coding RNA 881)

LOC101928236 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.584 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VEPH1	NM_001167912.2	c.2011-5623A>G		intron_variant	Intron 11 of 13	ENST00000362010.7	NP_001161384.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VEPH1	ENST00000362010.7	c.2011-5623A>G		intron_variant	Intron 11 of 13	1	NM_001167912.2	ENSP00000354919.2

Frequencies

GnomAD3 genomes AF: 0.452 AC: 68615 AN: 151908 Hom.: 16391 Cov.: 31

Gnomad AFR AF: 0.304

Gnomad AMI AF: 0.651

Gnomad AMR AF: 0.594

Gnomad ASJ AF: 0.450

Gnomad EAS AF: 0.421

Gnomad SAS AF: 0.348

Gnomad FIN AF: 0.432

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.520

Gnomad OTH AF: 0.461

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

GnomAD4 genome AF: 0.452 AC: 68659 AN: 152026 Hom.: 16404 Cov.: 31 AF XY: 0.448 AC XY: 33299 AN XY: 74334

African (AFR) AF: 0.304 AC: 12598 AN: 41472

American (AMR) AF: 0.594 AC: 9068 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.450 AC: 1563 AN: 3470

East Asian (EAS) AF: 0.421 AC: 2178 AN: 5174

South Asian (SAS) AF: 0.347 AC: 1669 AN: 4814

European-Finnish (FIN) AF: 0.432 AC: 4566 AN: 10560

Middle Eastern (MID) AF: 0.337 AC: 99 AN: 294

European-Non Finnish (NFE) AF: 0.520 AC: 35350 AN: 67956

Other (OTH) AF: 0.464 AC: 976 AN: 2104

Alfa AF: 0.492 Hom.: 5195

Bravo AF: 0.459

Asia WGS AF: 0.391 AC: 1361 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.8
DANN	Benign	0.47
PhyloP100		-0.39
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1403105; hg19: chr3-157010086;