NM_001167912.2:c.529+14335G>A

Variant names:

• chr3-157445846-C-T
• rs16827657
• NM_001167912.2:c.529+14335G>A

Variant summary

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

The NM_001167912.2(VEPH1):​c.529+14335G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.173 in 151,988 control chromosomes in the GnomAD database, including 4,718 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 0.17 (4718 hom., cov: 32)
• Consequence: VEPH1 NM_001167912.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.251
• Publications: 3 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 (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.443 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VEPH1	NM_001167912.2	c.529+14335G>A		intron_variant	Intron 4 of 13	ENST00000362010.7	NP_001161384.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VEPH1	ENST00000362010.7	c.529+14335G>A		intron_variant	Intron 4 of 13	1	NM_001167912.2	ENSP00000354919.2
VEPH1	ENST00000392833.6	c.529+14335G>A		intron_variant	Intron 4 of 12	1		ENSP00000376578.2
VEPH1	ENST00000392832.6	c.529+14335G>A		intron_variant	Intron 4 of 13	2		ENSP00000376577.2
VEPH1	ENST00000479987.5	c.193+14335G>A		intron_variant	Intron 3 of 3	3		ENSP00000418963.1

Frequencies

GnomAD3 genomes AF: 0.173 AC: 26247 AN: 151870 Hom.: 4699 Cov.: 32

Gnomad AFR AF: 0.448

Gnomad AMI AF: 0.0186

Gnomad AMR AF: 0.0776

Gnomad ASJ AF: 0.0769

Gnomad EAS AF: 0.165

Gnomad SAS AF: 0.258

Gnomad FIN AF: 0.0561

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.0487

Gnomad OTH AF: 0.129

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

GnomAD4 genome AF: 0.173 AC: 26310 AN: 151988 Hom.: 4718 Cov.: 32 AF XY: 0.172 AC XY: 12811 AN XY: 74288

African (AFR) AF: 0.448 AC: 18552 AN: 41386

American (AMR) AF: 0.0773 AC: 1180 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.0769 AC: 267 AN: 3470

East Asian (EAS) AF: 0.164 AC: 849 AN: 5170

South Asian (SAS) AF: 0.257 AC: 1237 AN: 4814

European-Finnish (FIN) AF: 0.0561 AC: 593 AN: 10566

Middle Eastern (MID) AF: 0.0782 AC: 23 AN: 294

European-Non Finnish (NFE) AF: 0.0488 AC: 3315 AN: 67994

Other (OTH) AF: 0.131 AC: 277 AN: 2110

Alfa AF: 0.0903 Hom.: 6144

Bravo AF: 0.183

Asia WGS AF: 0.227 AC: 791 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.0
DANN	Benign	0.50
PhyloP100		0.25
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: rs16827657; hg19: chr3-157163635;