rs1378796

Variant names:

• chr3-157413999-A-C
• rs1378796
• NM_001167912.2:c.788T>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.788T>G​(p.Val263Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.115 in 1,613,318 control chromosomes in the GnomAD database, including 13,373 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.14 (1719 hom., cov: 32)
  • Exomes 𝑓: 0.11 (11654 hom.)
• Consequence: VEPH1 NM_001167912.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.230
• Publications: 17 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.004198402).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.278 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VEPH1	NM_001167912.2	c.788T>G	p.Val263Gly	missense_variant	Exon 6 of 14	ENST00000362010.7	NP_001161384.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VEPH1	ENST00000362010.7	c.788T>G	p.Val263Gly	missense_variant	Exon 6 of 14	1	NM_001167912.2	ENSP00000354919.2

Frequencies

GnomAD3 genomes AF: 0.137 AC: 20810 AN: 151940 Hom.: 1712 Cov.: 32

Gnomad AFR AF: 0.202

Gnomad AMI AF: 0.0408

Gnomad AMR AF: 0.0736

Gnomad ASJ AF: 0.0896

Gnomad EAS AF: 0.242

Gnomad SAS AF: 0.290

Gnomad FIN AF: 0.151

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.0952

Gnomad OTH AF: 0.114

GnomAD2 exomes AF: 0.142 AC: 35578 AN: 250996 AF XY: 0.147

Gnomad AFR exome AF: 0.204

Gnomad AMR exome AF: 0.0977

Gnomad ASJ exome AF: 0.0900

Gnomad EAS exome AF: 0.242

Gnomad FIN exome AF: 0.154

Gnomad NFE exome AF: 0.0965

Gnomad OTH exome AF: 0.119

GnomAD4 exome AF: 0.113 AC: 164764 AN: 1461260 Hom.: 11654 Cov.: 32 AF XY: 0.118 AC XY: 85681 AN XY: 726928

African (AFR) AF: 0.200 AC: 6700 AN: 33434

American (AMR) AF: 0.0946 AC: 4225 AN: 44654

Ashkenazi Jewish (ASJ) AF: 0.0862 AC: 2251 AN: 26116

East Asian (EAS) AF: 0.266 AC: 10550 AN: 39680

South Asian (SAS) AF: 0.278 AC: 23974 AN: 86230

European-Finnish (FIN) AF: 0.151 AC: 8048 AN: 53378

Middle Eastern (MID) AF: 0.123 AC: 708 AN: 5762

European-Non Finnish (NFE) AF: 0.0906 AC: 100678 AN: 1111644

Other (OTH) AF: 0.126 AC: 7630 AN: 60362

GnomAD4 genome AF: 0.137 AC: 20850 AN: 152058 Hom.: 1719 Cov.: 32 AF XY: 0.141 AC XY: 10490 AN XY: 74306

African (AFR) AF: 0.202 AC: 8384 AN: 41476

American (AMR) AF: 0.0737 AC: 1125 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.0896 AC: 311 AN: 3470

East Asian (EAS) AF: 0.242 AC: 1249 AN: 5162

South Asian (SAS) AF: 0.290 AC: 1395 AN: 4804

European-Finnish (FIN) AF: 0.151 AC: 1595 AN: 10588

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.0953 AC: 6476 AN: 67976

Other (OTH) AF: 0.118 AC: 249 AN: 2110

Alfa AF: 0.109 Hom.: 4784

Bravo AF: 0.130

TwinsUK AF: 0.0863 AC: 320

ALSPAC AF: 0.0893 AC: 344

ESP6500AA AF: 0.199 AC: 875

ESP6500EA AF: 0.0934 AC: 803

ExAC AF: 0.148 AC: 17933

Asia WGS AF: 0.274 AC: 952 AN: 3478

EpiCase AF: 0.0978

EpiControl AF: 0.0942

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.043
BayesDel_addAF	Benign	-0.71	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	15
DANN	Benign	0.78
DEOGEN2	Benign	0.012	.;T;T
Eigen	Benign	-1.1
Eigen_PC	Benign	-0.96
FATHMM_MKL	Benign	0.0086	N
LIST_S2	Benign	0.016	T;.;T
MetaRNN	Benign	0.0042	T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	-1.7	N;N;N
PhyloP100		0.23
PrimateAI	Benign	0.29	T
PROVEAN	Benign	1.2	N;N;N
REVEL	Benign	0.055
Sift	Benign	0.46	T;T;T
Sift4G	Benign	0.65	T;T;T
Polyphen		0.0	B;B;B
Vest4		0.076
MPC		0.046
ClinPred		0.00052	T
GERP RS		4.1
Varity_R		0.038
gMVP		0.070
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: rs1378796; hg19: chr3-157131788; COSMIC: COSV62876919;