7-12353684-C-T

Variant names:

• chr7-12353684-C-T
• rs7809990
• NM_001135924.3:c.3746-1971G>A

Variant summary

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

The NM_001135924.3(VWDE):​c.3746-1971G>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
• 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.949 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.3746-1971G>A		intron	N/A	NP_001129396.1
	VWDE	NM_001346972.2		c.3401-1971G>A		intron	N/A	NP_001333901.1
	VWDE	NM_001346973.2		c.2936-1971G>A		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.3746-1971G>A		intron	N/A	ENSP00000275358.3
	VWDE	ENST00000452576.6	TSL:1	n.*509+131G>A		intron	N/A	ENSP00000401687.2
	VWDE	ENST00000644150.1		c.358+666G>A		intron	N/A	ENSP00000495749.1

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

African (AFR) AF: 1.00 AC: 2 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 1.00 AC: 8 AN: 8

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.957 AC: 39769 AN: 41540

American (AMR) AF: 0.918 AC: 14042 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.932 AC: 3237 AN: 3472

East Asian (EAS) AF: 0.809 AC: 4181 AN: 5168

South Asian (SAS) AF: 0.852 AC: 4110 AN: 4822

European-Finnish (FIN) AF: 0.904 AC: 9564 AN: 10580

Middle Eastern (MID) AF: 0.878 AC: 258 AN: 294

European-Non Finnish (NFE) AF: 0.896 AC: 60927 AN: 68024

Other (OTH) AF: 0.908 AC: 1922 AN: 2116

Alfa AF: 0.897 Hom.: 30830

Bravo AF: 0.915

Asia WGS AF: 0.858 AC: 2985 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	7.4
DANN	Benign	0.67
PhyloP100		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: rs7809990; hg19: chr7-12393310;