rs10249315

Positions:

• chr7-12353271-T-C

Variant summary

Our verdict is Benign. Variant got -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

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 Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VWDE	NM_001135924.3	c.3746-1558A>G		intron_variant		ENST00000275358.8	NP_001129396.1
VWDE	NM_001346972.2	c.3401-1558A>G		intron_variant			NP_001333901.1
VWDE	NM_001346973.2	c.2936-1558A>G		intron_variant			NP_001333902.1
VWDE	NR_144534.2	n.4567+544A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VWDE	ENST00000275358.8	c.3746-1558A>G		intron_variant		5	NM_001135924.3	ENSP00000275358	P1
VWDE	ENST00000452576.6	c.*509+544A>G		intron_variant, NMD_transcript_variant		1		ENSP00000401687
VWDE	ENST00000644150.1	c.358+1079A>G		intron_variant				ENSP00000495749
VWDE	ENST00000521169.5	c.*2124-1558A>G		intron_variant, NMD_transcript_variant		5		ENSP00000428810

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

Gnomad4 AFR AF: 0.850

Gnomad4 AMR AF: 0.920

Gnomad4 ASJ AF: 0.939

Gnomad4 EAS AF: 0.809

Gnomad4 SAS AF: 0.853

Gnomad4 FIN AF: 0.905

Gnomad4 NFE AF: 0.898

Gnomad4 OTH AF: 0.896

Alfa AF: 0.892 Hom.: 27831

Bravo AF: 0.884

Asia WGS AF: 0.851 AC: 2960 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	5.6
DANN	Benign	0.48
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs10249315; hg19: chr7-12392897; COSMIC: COSV51734259;