Genetic Variant VWCE:p.Ala947Thr (chr11-61258704-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_152718.2(VWCE):c.2839G>A(p.Ala947Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000137 in 1,240,114 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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: 0.000014 ( 0 hom. )

Consequence

VWCE
NM_152718.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.280

Publications

0 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.024466723).

BP6

Variant 11-61258704-C-T is Benign according to our data. Variant chr11-61258704-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2614839.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152718.2. 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
	VWCE	NM_152718.2	MANE Select	c.2839G>A	p.Ala947Thr	missense	Exon 20 of 20	NP_689931.2	Q96DN2-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
VWCE	ENST00000335613.10	TSL:1 MANE Select	c.2839G>A	p.Ala947Thr	missense	Exon 20 of 20	ENSP00000334186.5	Q96DN2-1
VWCE	ENST00000301770.10	TSL:1	n.*2236G>A		non_coding_transcript_exon	Exon 20 of 20	ENSP00000301770.6	Q96DN2-2
VWCE	ENST00000301770.10	TSL:1	n.*2236G>A		3_prime_UTR	Exon 20 of 20	ENSP00000301770.6	Q96DN2-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.0000137

AC:

AN:

1240114

Hom.:

Cov.:

AF XY:

0.0000150

AC XY:

AN XY:

598228

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26698

American (AMR)

AF:

0.00

AC:

AN:

21346

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

16952

East Asian (EAS)

AF:

0.00

AC:

AN:

33716

South Asian (SAS)

AF:

0.00

AC:

AN:

39692

European-Finnish (FIN)

AF:

0.00

AC:

AN:

44650

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4898

European-Non Finnish (NFE)

AF:

0.0000170

AC:

AN:

1001702

Other (OTH)

AF:

0.00

AC:

AN:

50460

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

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

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.064

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.67

CADD

Benign

0.041

(source)

DANN

Benign

0.11

DEOGEN2

Benign

0.013

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.0018

LIST_S2

Benign

0.55

M_CAP

Benign

0.011

MetaRNN

Benign

0.024

MetaSVM

Benign

-0.98

MutationAssessor

Benign

-0.63

PhyloP100

-0.28

PrimateAI

Benign

0.26

PROVEAN

Benign

0.31

REVEL

Benign

0.023

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.017

MutPred

0.042

Gain of glycosylation at A947 (P = 0.0065)

MVP

0.030

MPC

0.20

ClinPred

0.026

GERP RS

-2.3

Varity_R

0.025

gMVP

0.11

Mutation Taster

=99/1

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