Genetic Variant NM_014909.5:c.40G>A (chr14-76762861-G-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_014909.5(VASH1):c.40G>A(p.Gly14Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000145 in 1,374,866 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G14C) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000015 ( 0 hom. )

Consequence

VASH1
NM_014909.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.81

Publications

0 publications found

Variant links:

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]

VASH1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.03810212).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014909.5. 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
	VASH1	NM_014909.5	MANE Select	c.40G>A	p.Gly14Ser	missense	Exon 1 of 7	NP_055724.1	Q7L8A9-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VASH1	ENST00000167106.9	TSL:1 MANE Select	c.40G>A	p.Gly14Ser	missense	Exon 1 of 7	ENSP00000167106.4	Q7L8A9-1
	VASH1	ENST00000554237.1	TSL:1	c.40G>A	p.Gly14Ser	missense	Exon 1 of 4	ENSP00000451613.1	Q7L8A9-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000145

AC:

AN:

1374866

Hom.:

Cov.:

AF XY:

0.00000296

AC XY:

AN XY:

675154

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30978

American (AMR)

AF:

0.00

AC:

AN:

32518

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22778

East Asian (EAS)

AF:

0.0000544

AC:

AN:

36786

South Asian (SAS)

AF:

0.00

AC:

AN:

71970

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49530

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5080

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1068514

Other (OTH)

AF:

0.00

AC:

AN:

56712

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.067

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.64

CADD

Benign

0.077

(source)

DANN

Benign

0.82

DEOGEN2

Benign

0.078

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.021

LIST_S2

Benign

0.42

M_CAP

Benign

0.0027

MetaRNN

Benign

0.038

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

PhyloP100

-2.8

PrimateAI

Benign

0.46

PROVEAN

Benign

0.41

REVEL

Benign

0.013

Sift

Benign

0.34

Sift4G

Benign

0.22

Polyphen

0.0

Vest4

0.10

MutPred

0.093

Gain of glycosylation at G14 (P = 0.0019)

MVP

0.068

MPC

0.55

ClinPred

0.082

GERP RS

-4.3

Varity_R

0.044

gMVP

0.089

Mutation Taster

=93/7

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over