Variant 1-20317664-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001039500.3(VWA5B1):c.698G>T(p.Cys233Phe) variant causes a missense change. The variant allele was found at a frequency of 0.000195 in 1,551,316 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00021 ( 0 hom., cov: 30)

Exomes 𝑓: 0.00019 ( 0 hom. )

Consequence

VWA5B1
NM_001039500.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.56

Variant links:

Genes affected

VWA5B1 (HGNC:26538): (von Willebrand factor A domain containing 5B1) Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

VWA5B1 links:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.39450157).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VWA5B1	NM_001039500.3 linkuse as main transcript	c.698G>T	p.Cys233Phe	missense_variant	5/22	ENST00000289815.13	NP_001034589.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VWA5B1	ENST00000289815.13 linkuse as main transcript	c.698G>T	p.Cys233Phe	missense_variant	5/22	5	NM_001039500.3	ENSP00000289815	A2	Q5TIE3-2
	ENST00000444923.1 linkuse as main transcript	n.85+5439C>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.000210

AC:

AN:

152096

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00137

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:

0.000132

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.000210

AC:

AN:

156946

Hom.:

AF XY:

0.000193

AC XY:

AN XY:

82850

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000816

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000148

Gnomad OTH exome

AF:

0.000907

GnomAD4 exome

AF:

0.000194

AC:

271

AN:

1399220

Hom.:

Cov.:

AF XY:

0.000159

AC XY:

110

AN XY:

690132

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000953

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:

0.000211

Gnomad4 OTH exome

AF:

0.000155

GnomAD4 genome

AF:

0.000210

AC:

AN:

152096

Hom.:

Cov.:

AF XY:

0.000215

AC XY:

AN XY:

74280

show subpopulations

Gnomad4 AFR

AF:

0.0000242

Gnomad4 AMR

AF:

0.00137

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000132

Gnomad4 OTH

AF:

0.000479

Alfa

AF:

0.0000387

Hom.:

Bravo

AF:

0.000336

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000314

AC:

ExAC

AF:

0.0000371

AC:

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 submitter

clinical testing

Ambry Genetics

May 27, 2022

The c.698G>T (p.C233F) alteration is located in exon 5 (coding exon 4) of the VWA5B1 gene. This alteration results from a G to T substitution at nucleotide position 698, causing the cysteine (C) at amino acid position 233 to be replaced by a phenylalanine (F). 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

0.31

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.37

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.080

T;.

Eigen

Uncertain

0.56

Eigen_PC

Uncertain

0.55

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.89

D;D

M_CAP

Benign

0.018

MetaRNN

Benign

0.39

T;T

MetaSVM

Benign

-1.2

MutationAssessor

Pathogenic

3.0

M;M

MutationTaster

Benign

0.95

D;D;D;D;D

PrimateAI

Uncertain

0.56

PROVEAN

Pathogenic

-6.9

D;D

REVEL

Benign

0.17

Sift

Uncertain

0.028

D;D

Sift4G

Benign

0.15

T;T

Polyphen

0.98

D;P

Vest4

0.64

MVP

0.50

ClinPred

0.36

GERP RS

4.9

Varity_R

0.58

gMVP

0.59

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over