Genetic Variant VWCE:p.Pro888Ser (chr11-61258881-G-A) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_152718.2(VWCE):c.2662C>T(p.Pro888Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000237 in 1,520,080 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/15 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

VWCE
NM_152718.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.49

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (MetaRNN=0.029792845).

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.2662C>T	p.Pro888Ser	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.2662C>T	p.Pro888Ser	missense	Exon 20 of 20	ENSP00000334186.5	Q96DN2-1
VWCE	ENST00000301770.10	TSL:1	n.*2059C>T		non_coding_transcript_exon	Exon 20 of 20	ENSP00000301770.6	Q96DN2-2
VWCE	ENST00000301770.10	TSL:1	n.*2059C>T		3_prime_UTR	Exon 20 of 20	ENSP00000301770.6	Q96DN2-2

Frequencies

GnomAD3 genomes

AF:

0.000125

AC:

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000458

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000564

AC:

AN:

177262

AF XY:

0.0000322

show subpopulations

Gnomad AFR exome

AF:

0.000522

Gnomad AMR exome

AF:

0.0000962

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000124

AC:

AN:

1367770

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

670540

show subpopulations

African (AFR)

AF:

0.000397

AC:

AN:

30210

American (AMR)

AF:

0.0000690

AC:

AN:

28968

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19882

East Asian (EAS)

AF:

0.00

AC:

AN:

38912

South Asian (SAS)

AF:

0.00

AC:

AN:

70150

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49870

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5322

European-Non Finnish (NFE)

AF:

9.36e-7

AC:

AN:

1068204

Other (OTH)

AF:

0.0000356

AC:

AN:

56252

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

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

AF:

0.000125

AC:

AN:

152310

Hom.:

Cov.:

AF XY:

0.0000671

AC XY:

AN XY:

74480

show subpopulations

African (AFR)

AF:

0.000457

AC:

AN:

41580

American (AMR)

AF:

0.00

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68016

Other (OTH)

AF:

0.00

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.000164

Hom.:

Bravo

AF:

0.000113

ESP6500AA

AF:

0.000908

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000587

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Uncertain significance

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

0.078

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.43

CADD

Benign

6.8

(source)

DANN

Benign

0.85

DEOGEN2

Benign

0.0094

Eigen

Benign

-0.79

Eigen_PC

Benign

-0.79

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.47

M_CAP

Benign

0.015

MetaRNN

Benign

0.030

PhyloP100

1.5

Sift4G

Benign

0.41

Vest4

0.089

MVP

0.030

ClinPred

0.011

GERP RS

3.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.031

Mutation Taster

=95/5

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over