rs10249315

Variant names:

• chr7-12353271-T-C
• rs10249315
• NM_001135924.3:c.3746-1558A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001135924.3(VWDE):​c.3746-1558A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.884 in 152,210 control chromosomes in the GnomAD database, including 59,583 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.

• Frequency: Genomes: 𝑓 0.88 (59583 hom., cov: 32)
• Consequence: VWDE NM_001135924.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.453
• Publications: 1 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.907 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VWDE	NM_001135924.3	MANE Select	c.3746-1558A>G		intron	N/A	NP_001129396.1
	VWDE	NM_001346972.2		c.3401-1558A>G		intron	N/A	NP_001333901.1
	VWDE	NM_001346973.2		c.2936-1558A>G		intron	N/A	NP_001333902.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VWDE	ENST00000275358.8	TSL:5 MANE Select	c.3746-1558A>G		intron	N/A	ENSP00000275358.3
	VWDE	ENST00000452576.6	TSL:1	n.*509+544A>G		intron	N/A	ENSP00000401687.2
	VWDE	ENST00000941987.1		c.3401-1558A>G		intron	N/A	ENSP00000612046.1

Frequencies

GnomAD3 genomes AF: 0.884 AC: 134493 AN: 152092 Hom.: 59552 Cov.: 32

Gnomad AFR AF: 0.850

Gnomad AMI AF: 0.940

Gnomad AMR AF: 0.919

Gnomad ASJ AF: 0.939

Gnomad EAS AF: 0.810

Gnomad SAS AF: 0.852

Gnomad FIN AF: 0.905

Gnomad MID AF: 0.908

Gnomad NFE AF: 0.898

Gnomad OTH AF: 0.895

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.884 AC: 134582 AN: 152210 Hom.: 59583 Cov.: 32 AF XY: 0.885 AC XY: 65824 AN XY: 74404

African (AFR) AF: 0.850 AC: 35281 AN: 41514

American (AMR) AF: 0.920 AC: 14060 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.939 AC: 3259 AN: 3470

East Asian (EAS) AF: 0.809 AC: 4178 AN: 5166

South Asian (SAS) AF: 0.853 AC: 4109 AN: 4816

European-Finnish (FIN) AF: 0.905 AC: 9596 AN: 10608

Middle Eastern (MID) AF: 0.908 AC: 267 AN: 294

European-Non Finnish (NFE) AF: 0.898 AC: 61083 AN: 68028

Other (OTH) AF: 0.896 AC: 1892 AN: 2112

Alfa AF: 0.893 Hom.: 31243

Bravo AF: 0.884

Asia WGS AF: 0.851 AC: 2960 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	5.6
DANN	Benign	0.48
PhyloP100		-0.45
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=100/0	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: rs10249315; hg19: chr7-12392897; COSMIC: COSV51734259;