NM_014909.5:c.398+540C>T

Variant names:

• chr14-76770591-C-T
• rs8006081
• NM_014909.5:c.398+540C>T

Variant summary

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

The NM_014909.5(VASH1):​c.398+540C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.759 in 151,986 control chromosomes in the GnomAD database, including 43,961 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 0.76 (43961 hom., cov: 31)
• Consequence: VASH1 NM_014909.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.119
• Publications: 1 publications found

Genes affected

VASH1 (HGNC:19964): (vasohibin 1) Enables actin binding activity and metallocarboxypeptidase activity. Involved in negative regulation of angiogenesis; negative regulation of blood vessel endothelial cell migration; and proteolysis. Acts upstream of or within several processes, including negative regulation of endothelial cell migration; negative regulation of endothelial cell proliferation; and negative regulation of lymphangiogenesis. Located in apical part of cell; endoplasmic reticulum; and extracellular space. Implicated in liver cirrhosis and portal hypertension. Biomarker of liver cirrhosis. [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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.774 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VASH1	NM_014909.5	c.398+540C>T		intron_variant	Intron 2 of 6	ENST00000167106.9	NP_055724.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VASH1	ENST00000167106.9	c.398+540C>T		intron_variant	Intron 2 of 6	1	NM_014909.5	ENSP00000167106.4
VASH1	ENST00000554237.1	c.398+540C>T		intron_variant	Intron 2 of 3	1		ENSP00000451613.1
VASH1	ENST00000553518.1	n.99+540C>T		intron_variant	Intron 1 of 3	3
VASH1	ENST00000556038.5	n.171+540C>T		intron_variant	Intron 1 of 4	5

Frequencies

GnomAD3 genomes AF: 0.758 AC: 115188 AN: 151868 Hom.: 43918 Cov.: 31

Gnomad AFR AF: 0.781

Gnomad AMI AF: 0.730

Gnomad AMR AF: 0.643

Gnomad ASJ AF: 0.719

Gnomad EAS AF: 0.681

Gnomad SAS AF: 0.776

Gnomad FIN AF: 0.817

Gnomad MID AF: 0.726

Gnomad NFE AF: 0.769

Gnomad OTH AF: 0.750

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

GnomAD4 genome AF: 0.759 AC: 115286 AN: 151986 Hom.: 43961 Cov.: 31 AF XY: 0.759 AC XY: 56397 AN XY: 74264

African (AFR) AF: 0.781 AC: 32372 AN: 41460

American (AMR) AF: 0.643 AC: 9821 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.719 AC: 2494 AN: 3468

East Asian (EAS) AF: 0.682 AC: 3512 AN: 5148

South Asian (SAS) AF: 0.775 AC: 3730 AN: 4810

European-Finnish (FIN) AF: 0.817 AC: 8635 AN: 10568

Middle Eastern (MID) AF: 0.729 AC: 213 AN: 292

European-Non Finnish (NFE) AF: 0.769 AC: 52253 AN: 67940

Other (OTH) AF: 0.751 AC: 1590 AN: 2116

Alfa AF: 0.763 Hom.: 5495

Bravo AF: 0.743

Asia WGS AF: 0.717 AC: 2495 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.0
DANN	Benign	0.34
PhyloP100		0.12
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: rs8006081; hg19: chr14-77236934;