12-95273561-C-T

Variant names:

• chr12-95273561-C-T
• rs4471514
• NM_017599.4:c.849-1181C>T

Variant summary

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

The NM_017599.4(VEZT):​c.849-1181C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.484 in 151,936 control chromosomes in the GnomAD database, including 18,149 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 0.48 (18149 hom., cov: 32)
• Consequence: VEZT NM_017599.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.195
• Publications: 2 publications found

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

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.562 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017599.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VEZT	NM_017599.4	MANE Select	c.849-1181C>T		intron	N/A	NP_060069.3
	VEZT	NM_001352088.2		c.918-1181C>T		intron	N/A	NP_001339017.1
	VEZT	NM_001352089.2		c.861-1181C>T		intron	N/A	NP_001339018.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VEZT	ENST00000436874.6	TSL:1 MANE Select	c.849-1181C>T		intron	N/A	ENSP00000410083.1
	VEZT	ENST00000397792.8	TSL:1	c.717-1181C>T		intron	N/A	ENSP00000380894.4
	VEZT	ENST00000546398.5	TSL:1	n.901-1181C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.484 AC: 73495 AN: 151818 Hom.: 18123 Cov.: 32

Gnomad AFR AF: 0.568

Gnomad AMI AF: 0.634

Gnomad AMR AF: 0.428

Gnomad ASJ AF: 0.522

Gnomad EAS AF: 0.429

Gnomad SAS AF: 0.494

Gnomad FIN AF: 0.317

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.471

Gnomad OTH AF: 0.497

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

GnomAD4 genome AF: 0.484 AC: 73568 AN: 151936 Hom.: 18149 Cov.: 32 AF XY: 0.475 AC XY: 35276 AN XY: 74244

African (AFR) AF: 0.568 AC: 23527 AN: 41428

American (AMR) AF: 0.428 AC: 6530 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.522 AC: 1811 AN: 3468

East Asian (EAS) AF: 0.429 AC: 2217 AN: 5170

South Asian (SAS) AF: 0.494 AC: 2381 AN: 4820

European-Finnish (FIN) AF: 0.317 AC: 3341 AN: 10556

Middle Eastern (MID) AF: 0.524 AC: 154 AN: 294

European-Non Finnish (NFE) AF: 0.471 AC: 31982 AN: 67920

Other (OTH) AF: 0.497 AC: 1047 AN: 2106

Alfa AF: 0.482 Hom.: 2308

Bravo AF: 0.495

Asia WGS AF: 0.484 AC: 1675 AN: 3462

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	13
DANN	Benign	0.73
PhyloP100		0.20
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: rs4471514; hg19: chr12-95667337;