Variant 11-61258755-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_152718.2(VWCE):c.2788A>G(p.Thr930Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000548 in 1,278,070 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. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

VWCE
NM_152718.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0140

Variant links:

Genes affected

VWCE (HGNC:26487): (von Willebrand factor C and EGF domains) Predicted to enable calcium ion binding activity. Involved in cellular response to virus. Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

VWCE links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.023913443).

BP6

Variant 11-61258755-T-C is Benign according to our data. Variant chr11-61258755-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2244082.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VWCE	NM_152718.2 linkuse as main transcript	c.2788A>G	p.Thr930Ala	missense_variant	20/20	ENST00000335613.10	NP_689931.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VWCE	ENST00000335613.10 linkuse as main transcript	c.2788A>G	p.Thr930Ala	missense_variant	20/20	1	NM_152718.2	ENSP00000334186	P1	Q96DN2-1
VWCE	ENST00000301770.10 linkuse as main transcript	c.*2185A>G		3_prime_UTR_variant, NMD_transcript_variant	20/20	1		ENSP00000301770		Q96DN2-2
VWCE	ENST00000535710.1 linkuse as main transcript	c.1183A>G	p.Thr395Ala	missense_variant	9/9	2		ENSP00000442570

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000670

AC:

AN:

149286

Hom.:

AF XY:

0.0000126

AC XY:

AN XY:

79662

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000854

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000548

AC:

AN:

1278070

Hom.:

Cov.:

AF XY:

0.00000484

AC XY:

AN XY:

619964

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:

0.000142

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 12, 2021

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.051

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.61

CADD

Benign

0.097

DANN

Benign

0.11

DEOGEN2

Benign

0.0022

T;T;T

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.0013

LIST_S2

Benign

0.36

T;T;T

M_CAP

Benign

0.012

MetaRNN

Benign

0.024

T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

-1.0

.;N;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.34

PROVEAN

Benign

0.030

.;N;N

REVEL

Benign

0.064

Sift

Benign

1.0

.;T;T

Sift4G

Benign

1.0

T;T;T

Polyphen

0.0

.;B;.

Vest4

0.010

MutPred

0.12

.;Loss of phosphorylation at T930 (P = 0.018);.;

MVP

0.040

MPC

0.20

ClinPred

0.016

GERP RS

1.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.026

gMVP

0.12

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