rs6967385

Variant names:

• chr7-12351693-G-C
• rs6967385
• NM_001135924.3:c.3766C>G

Your query was ambiguous. Multiple possible variants found:

• chr7-12351693-G-C
• chr7-12351693-G-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000275358.8(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. 17/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: VWDE ENST00000275358.8 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.131
• Publications: 29 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000275358.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VWDE	NM_001135924.3	MANE Select	c.3766C>G	p.Gln1256Glu	missense	Exon 19 of 29	NP_001129396.1
	VWDE	NM_001346972.2		c.3421C>G	p.Gln1141Glu	missense	Exon 17 of 27	NP_001333901.1
	VWDE	NM_001346973.2		c.2956C>G	p.Gln986Glu	missense	Exon 17 of 27	NP_001333902.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VWDE	ENST00000275358.8	TSL:5 MANE Select	c.3766C>G	p.Gln1256Glu	missense	Exon 19 of 29	ENSP00000275358.3
	VWDE	ENST00000452576.6	TSL:1	n.*530C>G		non_coding_transcript_exon	Exon 20 of 30	ENSP00000401687.2
	VWDE	ENST00000452576.6	TSL:1	n.*530C>G		3_prime_UTR	Exon 20 of 30	ENSP00000401687.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
Eigen	Benign	-1.9
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.0023	N
LIST_S2	Benign	0.18	T
M_CAP	Benign	0.0042	T
MetaRNN	Benign	0.031	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-2.1	N
PhyloP100		-0.13
PrimateAI	Benign	0.29	T
PROVEAN	Benign	0.63	N
REVEL	Benign	0.14
Sift	Benign	1.0	T
Sift4G	Benign	0.98	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
PromoterAI		0.0036	Neutral
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		3.6
Varity_R		0.038
gMVP		0.46
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs6967385; hg19: chr7-12391319;