rs17023875

chr12-95273067-T-C

Variant summary

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

The NM_017599.4(VEZT):c.849-1675T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.11 in 152,174 control chromosomes in the GnomAD database, including 1,339 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 0.11 (1339 hom., cov: 32)
• Consequence: VEZT NM_017599.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.49

Genes affected

VEZT (HGNC:18258): (vezatin, adherens junctions transmembrane protein) This gene encodes a transmembrane protein which has been localized to adherens junctions and shown to bind to myosin VIIA. Examination of expression of this gene in gastric cancer tissues have shown that expression is decreased which appears to be related to hypermethylation of the promoter. Expression of this gene may also be inhibited by binding of a specific microRNA to a target sequence in the 3' UTR of the transcripts. A pseudogene of this gene is located on the X chromosome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.226 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VEZT	NM_017599.4	c.849-1675T>C		intron_variant		ENST00000436874.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VEZT	ENST00000436874.6	c.849-1675T>C		intron_variant		1	NM_017599.4	P1

Frequencies

GnomAD3 genomes AF: 0.110 AC: 16763 AN: 152056 Hom.: 1336 Cov.: 32

Gnomad AFR AF: 0.230

Gnomad AMI AF: 0.118

Gnomad AMR AF: 0.0668

Gnomad ASJ AF: 0.0582

Gnomad EAS AF: 0.00288

Gnomad SAS AF: 0.136

Gnomad FIN AF: 0.0318

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0686

Gnomad OTH AF: 0.103

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

GnomAD4 genome AF: 0.110 AC: 16781 AN: 152174 Hom.: 1339 Cov.: 32 AF XY: 0.108 AC XY: 8025 AN XY: 74414

Gnomad4 AFR AF: 0.230

Gnomad4 AMR AF: 0.0666

Gnomad4 ASJ AF: 0.0582

Gnomad4 EAS AF: 0.00289

Gnomad4 SAS AF: 0.137

Gnomad4 FIN AF: 0.0318

Gnomad4 NFE AF: 0.0686

Gnomad4 OTH AF: 0.102

Alfa AF: 0.0900 Hom.: 139

Bravo AF: 0.116

Asia WGS AF: 0.0640 AC: 224 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
Cadd	Benign	9.9
Dann	Benign	0.89

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: rs17023875; hg19: chr12-95666843;