14-76762892-C-A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_014909.5(VASH1):​c.71C>A​(p.Ala24Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00055 in 1,556,930 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00024 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00058 ( 2 hom. )

Consequence

VASH1
NM_014909.5 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.891
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.035580963).
BS2
High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
VASH1NM_014909.5 linkuse as main transcriptc.71C>A p.Ala24Asp missense_variant 1/7 ENST00000167106.9 NP_055724.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
VASH1ENST00000167106.9 linkuse as main transcriptc.71C>A p.Ala24Asp missense_variant 1/71 NM_014909.5 ENSP00000167106 P1Q7L8A9-1
VASH1ENST00000554237.1 linkuse as main transcriptc.71C>A p.Ala24Asp missense_variant 1/41 ENSP00000451613 Q7L8A9-2

Frequencies

GnomAD3 genomes
AF:
0.000237
AC:
36
AN:
152180
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000724
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000654
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000470
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000231
AC:
44
AN:
190368
Hom.:
0
AF XY:
0.000174
AC XY:
18
AN XY:
103290
show subpopulations
Gnomad AFR exome
AF:
0.0000856
Gnomad AMR exome
AF:
0.0000399
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000439
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000381
Gnomad OTH exome
AF:
0.000661
GnomAD4 exome
AF:
0.000584
AC:
821
AN:
1404750
Hom.:
2
Cov.:
30
AF XY:
0.000581
AC XY:
403
AN XY:
694162
show subpopulations
Gnomad4 AFR exome
AF:
0.0000940
Gnomad4 AMR exome
AF:
0.0000811
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000135
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000702
Gnomad4 OTH exome
AF:
0.000845
GnomAD4 genome
AF:
0.000237
AC:
36
AN:
152180
Hom.:
0
Cov.:
33
AF XY:
0.000215
AC XY:
16
AN XY:
74340
show subpopulations
Gnomad4 AFR
AF:
0.0000724
Gnomad4 AMR
AF:
0.0000654
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000470
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000328
Hom.:
0
Bravo
AF:
0.000344
TwinsUK
AF:
0.00108
AC:
4
ALSPAC
AF:
0.00234
AC:
9
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000583
AC:
5
ExAC
AF:
0.000142
AC:
17

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsApr 28, 2022The c.71C>A (p.A24D) alteration is located in exon 1 (coding exon 1) of the VASH1 gene. This alteration results from a C to A substitution at nucleotide position 71, causing the alanine (A) at amino acid position 24 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.14
BayesDel_addAF
Benign
-0.41
T
BayesDel_noAF
Benign
-0.37
CADD
Benign
13
DANN
Uncertain
0.98
DEOGEN2
Benign
0.091
T;.
Eigen
Benign
-0.72
Eigen_PC
Benign
-0.72
FATHMM_MKL
Benign
0.31
N
LIST_S2
Benign
0.45
T;T
M_CAP
Benign
0.013
T
MetaRNN
Benign
0.036
T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.0
N;N
MutationTaster
Benign
1.0
N;N
PrimateAI
Uncertain
0.52
T
PROVEAN
Benign
-0.33
N;N
REVEL
Benign
0.050
Sift
Benign
0.11
T;T
Sift4G
Benign
0.56
T;T
Polyphen
0.13
B;P
Vest4
0.17
MVP
0.068
MPC
0.84
ClinPred
0.012
T
GERP RS
3.3
Varity_R
0.15
gMVP
0.47

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs369529500; hg19: chr14-77229235; API