Variant 1-1436947-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_022834.5(VWA1):c.94C>G(p.Arg32Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000249 in 1,607,494 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

VWA1
NM_022834.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.30

Variant links:

Genes affected

VWA1 (HGNC:30910): (von Willebrand factor A domain containing 1) VWA1 belongs to the von Willebrand factor (VWF; MIM 613160) A (VWFA) domain superfamily of extracellular matrix proteins and appears to play a role in cartilage structure and function (Fitzgerald et al., 2002 [PubMed 12062410]).[supplied by OMIM, Nov 2010]

VWA1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.07145396).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VWA1	NM_022834.5 link	c.94C>G	p.Arg32Gly	missense_variant	Exon 2 of 3	ENST00000476993.2	NP_073745.2	Q6PCB0-1
VWA1	NM_199121.3 link	c.74-375C>G		intron_variant	Intron 1 of 2		NP_954572.2	Q6PCB0-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
VWA1	ENST00000476993.2 link	c.94C>G	p.Arg32Gly	missense_variant	Exon 2 of 3	1	NM_022834.5	ENSP00000417185.1	Q6PCB0-1
VWA1	ENST00000471398.1 link	c.214C>G	p.Arg72Gly	missense_variant	Exon 2 of 2	3		ENSP00000464343.1	J3QRR0
VWA1	ENST00000495558 link	c.-12C>G		5_prime_UTR_variant	Exon 2 of 2	2		ENSP00000463643.1	J3QLP3
VWA1	ENST00000338660.5 link	c.74-375C>G		intron_variant	Intron 1 of 2	2		ENSP00000423404.1	Q6PCB0-3

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1455278

Hom.:

Cov.:

AF XY:

0.00000277

AC XY:

AN XY:

723194

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152216

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74368

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000101

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.060

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Benign

0.86

DEOGEN2

Benign

0.13

T;.

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.084

LIST_S2

Benign

0.39

T;T

M_CAP

Benign

0.064

MetaRNN

Benign

0.071

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

N;.

PrimateAI

Uncertain

0.57

PROVEAN

Benign

-1.1

N;.

REVEL

Benign

0.014

Sift

Benign

0.055

T;.

Sift4G

Benign

0.093

T;T

Polyphen

0.0010

B;.

Vest4

0.12

MutPred

0.31

Gain of glycosylation at S29 (P = 0.0719);.;

MVP

0.27

MPC

0.039

ClinPred

0.052

GERP RS

1.7

Varity_R

0.087

gMVP

0.43

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over