7-12353684-C-T

Position:

• chr7-12353684-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001135924.3(VWDE):​c.3746-1971G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.912 in 152,232 control chromosomes in the GnomAD database, including 63,465 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 0.91 (63460 hom., cov: 31)
  • Exomes 𝑓: 1.0 (5 hom.)
• Consequence: VWDE NM_001135924.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.02

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.949 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VWDE	NM_001135924.3	c.3746-1971G>A		intron_variant		ENST00000275358.8	NP_001129396.1
VWDE	NM_001346972.2	c.3401-1971G>A		intron_variant			NP_001333901.1
VWDE	NM_001346973.2	c.2936-1971G>A		intron_variant			NP_001333902.1
VWDE	NR_144534.2	n.4567+131G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VWDE	ENST00000275358.8	c.3746-1971G>A		intron_variant		5	NM_001135924.3	ENSP00000275358	P1
VWDE	ENST00000452576.6	c.*509+131G>A		intron_variant, NMD_transcript_variant		1		ENSP00000401687
VWDE	ENST00000644150.1	c.358+666G>A		intron_variant				ENSP00000495749
VWDE	ENST00000521169.5	c.*2124-1971G>A		intron_variant, NMD_transcript_variant		5		ENSP00000428810

Frequencies

GnomAD3 genomes AF: 0.912 AC: 138749 AN: 152104 Hom.: 63408 Cov.: 31

Gnomad AFR AF: 0.958

Gnomad AMI AF: 0.931

Gnomad AMR AF: 0.918

Gnomad ASJ AF: 0.932

Gnomad EAS AF: 0.810

Gnomad SAS AF: 0.851

Gnomad FIN AF: 0.904

Gnomad MID AF: 0.880

Gnomad NFE AF: 0.896

Gnomad OTH AF: 0.908

GnomAD4 exome AF: 1.00 AC: 10 AN: 10 Hom.: 5 AF XY: 1.00 AC XY: 6 AN XY: 6

Gnomad4 AFR exome AF: 1.00

Gnomad4 NFE exome AF: 1.00

GnomAD4 genome AF: 0.912 AC: 138859 AN: 152222 Hom.: 63460 Cov.: 31 AF XY: 0.911 AC XY: 67813 AN XY: 74426

Gnomad4 AFR AF: 0.957

Gnomad4 AMR AF: 0.918

Gnomad4 ASJ AF: 0.932

Gnomad4 EAS AF: 0.809

Gnomad4 SAS AF: 0.852

Gnomad4 FIN AF: 0.904

Gnomad4 NFE AF: 0.896

Gnomad4 OTH AF: 0.908

Alfa AF: 0.896 Hom.: 27341

Bravo AF: 0.915

Asia WGS AF: 0.858 AC: 2985 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	7.4
DANN	Benign	0.67

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: rs7809990; hg19: chr7-12393310;