rs17165936

Variant names:

• chr7-12375099-G-A
• rs17165936
• NM_001135924.3:c.1153C>T

Your query was ambiguous. Multiple possible variants found:

• chr7-12375099-G-A
• chr7-12375099-G-C

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_001135924.3(VWDE):​c.1153C>T​(p.Arg385*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.125 in 1,550,886 control chromosomes in the GnomAD database, including 13,149 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: 𝑓 0.14 (1619 hom., cov: 32)
  • Exomes 𝑓: 0.12 (11530 hom.)
• Consequence: VWDE NM_001135924.3 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.84
• Publications: 21 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: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.194 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001135924.3. 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
	VWDE	NM_001135924.3	MANE Select	c.1153C>T	p.Arg385*	stop_gained	Exon 8 of 29	NP_001129396.1	Q8N2E2-1
	VWDE	NM_001346972.2		c.1153C>T	p.Arg385*	stop_gained	Exon 8 of 27	NP_001333901.1
	VWDE	NM_001346973.2		c.688C>T	p.Arg230*	stop_gained	Exon 8 of 27	NP_001333902.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VWDE	ENST00000275358.8	TSL:5 MANE Select	c.1153C>T	p.Arg385*	stop_gained	Exon 8 of 29	ENSP00000275358.3	Q8N2E2-1
	VWDE	ENST00000452576.6	TSL:1	n.1153C>T		non_coding_transcript_exon	Exon 8 of 30	ENSP00000401687.2	J3KQJ9
	VWDE	ENST00000941987.1		c.1153C>T	p.Arg385*	stop_gained	Exon 8 of 27	ENSP00000612046.1

Frequencies

GnomAD3 genomes AF: 0.136 AC: 20675 AN: 151890 Hom.: 1618 Cov.: 32

Gnomad AFR AF: 0.194

Gnomad AMI AF: 0.0987

Gnomad AMR AF: 0.0787

Gnomad ASJ AF: 0.0866

Gnomad EAS AF: 0.195

Gnomad SAS AF: 0.206

Gnomad FIN AF: 0.119

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.111

Gnomad OTH AF: 0.108

GnomAD2 exomes AF: 0.124 AC: 19531 AN: 156890 AF XY: 0.130

Gnomad AFR exome AF: 0.191

Gnomad AMR exome AF: 0.0571

Gnomad ASJ exome AF: 0.0947

Gnomad EAS exome AF: 0.196

Gnomad FIN exome AF: 0.112

Gnomad NFE exome AF: 0.115

Gnomad OTH exome AF: 0.0979

GnomAD4 exome AF: 0.124 AC: 172887 AN: 1398878 Hom.: 11530 Cov.: 32 AF XY: 0.125 AC XY: 86490 AN XY: 689944

African (AFR) AF: 0.200 AC: 6309 AN: 31570

American (AMR) AF: 0.0620 AC: 2212 AN: 35704

Ashkenazi Jewish (ASJ) AF: 0.0902 AC: 2269 AN: 25162

East Asian (EAS) AF: 0.218 AC: 7797 AN: 35698

South Asian (SAS) AF: 0.194 AC: 15338 AN: 79210

European-Finnish (FIN) AF: 0.113 AC: 5589 AN: 49290

Middle Eastern (MID) AF: 0.109 AC: 623 AN: 5690

European-Non Finnish (NFE) AF: 0.117 AC: 125671 AN: 1078572

Other (OTH) AF: 0.122 AC: 7079 AN: 57982

GnomAD4 genome AF: 0.136 AC: 20693 AN: 152008 Hom.: 1619 Cov.: 32 AF XY: 0.137 AC XY: 10181 AN XY: 74308

African (AFR) AF: 0.194 AC: 8057 AN: 41450

American (AMR) AF: 0.0787 AC: 1200 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.0866 AC: 300 AN: 3464

East Asian (EAS) AF: 0.195 AC: 1008 AN: 5164

South Asian (SAS) AF: 0.205 AC: 987 AN: 4826

European-Finnish (FIN) AF: 0.119 AC: 1254 AN: 10568

Middle Eastern (MID) AF: 0.112 AC: 33 AN: 294

European-Non Finnish (NFE) AF: 0.111 AC: 7537 AN: 67966

Other (OTH) AF: 0.108 AC: 227 AN: 2108

Alfa AF: 0.118 Hom.: 3005

Bravo AF: 0.135

TwinsUK AF: 0.112 AC: 416

ALSPAC AF: 0.122 AC: 471

ESP6500AA AF: 0.209 AC: 289

ESP6500EA AF: 0.114 AC: 362

ExAC AF: 0.141 AC: 3476

Asia WGS AF: 0.178 AC: 617 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.056	T
BayesDel_noAF	Pathogenic	0.29
CADD	Pathogenic	36
DANN	Uncertain	1.0
Eigen	Uncertain	0.31
Eigen_PC	Benign	0.061
FATHMM_MKL	Benign	0.28	N
PhyloP100		1.8
Vest4		0.070
GERP RS		3.8
Mutation Taster		=144/56	polymorphism (auto)

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: rs17165936; hg19: chr7-12414725; COSMIC: COSV51725678; COSMIC: COSV51725678;