3-157428518-A-T

Position:

• chr3-157428518-A-T

Variant summary

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

The NM_001167912.2(VEPH1):​c.530-30T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.485 in 1,600,918 control chromosomes in the GnomAD database, including 192,038 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. There are indicators that this mutation may affect the branch point..

• Frequency:
  • Genomes: 𝑓 0.44 (15869 hom., cov: 32)
  • Exomes 𝑓: 0.49 (176169 hom.)
• Consequence: VEPH1 NM_001167912.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0650

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]

VEPH1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: This place is a probable branch point but likely benign (scored 2 / 10). Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.568 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VEPH1	NM_001167912.2	c.530-30T>A		intron_variant		ENST00000362010.7	NP_001161384.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VEPH1	ENST00000362010.7	c.530-30T>A		intron_variant		1	NM_001167912.2	ENSP00000354919.2

Frequencies

GnomAD3 genomes AF: 0.445 AC: 67536 AN: 151882 Hom.: 15859 Cov.: 32

Gnomad AFR AF: 0.288

Gnomad AMI AF: 0.554

Gnomad AMR AF: 0.578

Gnomad ASJ AF: 0.479

Gnomad EAS AF: 0.481

Gnomad SAS AF: 0.372

Gnomad FIN AF: 0.467

Gnomad MID AF: 0.456

Gnomad NFE AF: 0.506

Gnomad OTH AF: 0.450

GnomAD3 exomes AF: 0.485 AC: 119351 AN: 246334 Hom.: 29935 AF XY: 0.480 AC XY: 64055 AN XY: 133332

Gnomad AFR exome AF: 0.281

Gnomad AMR exome AF: 0.617

Gnomad ASJ exome AF: 0.473

Gnomad EAS exome AF: 0.473

Gnomad SAS exome AF: 0.365

Gnomad FIN exome AF: 0.479

Gnomad NFE exome AF: 0.509

Gnomad OTH exome AF: 0.489

GnomAD4 exome AF: 0.489 AC: 709119 AN: 1448916 Hom.: 176169 Cov.: 28 AF XY: 0.486 AC XY: 350288 AN XY: 720874

Gnomad4 AFR exome AF: 0.278

Gnomad4 AMR exome AF: 0.613

Gnomad4 ASJ exome AF: 0.476

Gnomad4 EAS exome AF: 0.485

Gnomad4 SAS exome AF: 0.362

Gnomad4 FIN exome AF: 0.477

Gnomad4 NFE exome AF: 0.503

Gnomad4 OTH exome AF: 0.469

GnomAD4 genome AF: 0.445 AC: 67572 AN: 152002 Hom.: 15869 Cov.: 32 AF XY: 0.445 AC XY: 33036 AN XY: 74268

Gnomad4 AFR AF: 0.288

Gnomad4 AMR AF: 0.578

Gnomad4 ASJ AF: 0.479

Gnomad4 EAS AF: 0.481

Gnomad4 SAS AF: 0.372

Gnomad4 FIN AF: 0.467

Gnomad4 NFE AF: 0.506

Gnomad4 OTH AF: 0.454

Alfa AF: 0.476 Hom.: 3364

Bravo AF: 0.447

Asia WGS AF: 0.445 AC: 1549 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.2
DANN	Benign	0.60
BranchPoint Hunter		2.0

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: rs1456099; hg19: chr3-157146307; COSMIC: COSV62882985; COSMIC: COSV62882985;