rs6967385

chr7-12351693-G-Cchr7-12351693-G-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001135924.3(VWDE):c.3766C>G(p.Gln1256Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q1256K) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: VWDE NM_001135924.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.131

Genes affected

VWDE (HGNC:21897): (von Willebrand factor D and EGF domains) Predicted to enable signaling receptor binding activity. Predicted to be involved in anatomical structure development. Predicted to be active in cell surface and extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.030693501).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VWDE	NM_001135924.3	c.3766C>G	p.Gln1256Glu	missense_variant	19/29	ENST00000275358.8
VWDE	NM_001346972.2	c.3421C>G	p.Gln1141Glu	missense_variant	17/27
VWDE	NM_001346973.2	c.2956C>G	p.Gln986Glu	missense_variant	17/27
VWDE	NR_144534.2	n.4588C>G		non_coding_transcript_exon_variant	20/30

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VWDE	ENST00000275358.8	c.3766C>G	p.Gln1256Glu	missense_variant	19/29	5	NM_001135924.3	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.056
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
Cadd	Benign	0.035
Dann	Benign	0.10
DEOGEN2	Benign	0.017	T;T;.
Eigen	Benign	-1.9
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.0023	N
LIST_S2	Benign	0.18	T;T;T
M_CAP	Benign	0.0042	T
MetaRNN	Benign	0.031	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-2.1	N;.;.
MutationTaster	Benign	1.0	P
PrimateAI	Benign	0.29	T
PROVEAN	Benign	0.63	N;.;.
REVEL	Benign	0.14
Sift	Benign	1.0	T;.;.
Sift4G	Benign	0.98	T;T;.
Polyphen		0.0	B;.;.
Vest4		0.025
MutPred		0.42		Gain of glycosylation at T1251 (P = 0.1596);.;.;
MVP		0.040
ClinPred		0.042	T
GERP RS		-1.1
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		3.6
Varity_R		0.038
gMVP		0.46

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

Other links and lift over

dbSNP: rs6967385; hg19: chr7-12391319;