rs2287067

Positions:

• chr7-12330907-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.*276A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.225 in 342,082 control chromosomes in the GnomAD database, including 11,295 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 0.28 (7567 hom., cov: 32)
  • Exomes 𝑓: 0.18 (3728 hom.)
• Consequence: VWDE NM_001135924.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0530

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=-0.76).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.508 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VWDE	NM_001135924.3	c.*276A>G		3_prime_UTR_variant	29/29	ENST00000275358.8	NP_001129396.1
VWDE	NM_001346972.2	c.*276A>G		3_prime_UTR_variant	27/27		NP_001333901.1
VWDE	NM_001346973.2	c.*276A>G		3_prime_UTR_variant	27/27		NP_001333902.1
VWDE	NR_144534.2	n.5871A>G		non_coding_transcript_exon_variant	30/30

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VWDE	ENST00000275358.8	c.*276A>G		3_prime_UTR_variant	29/29	5	NM_001135924.3	ENSP00000275358	P1
VWDE	ENST00000485526.1	n.553A>G		non_coding_transcript_exon_variant	2/2	2
VWDE	ENST00000452576.6			downstream_gene_variant		1		ENSP00000401687
VWDE	ENST00000521169.5			downstream_gene_variant		5		ENSP00000428810

Frequencies

GnomAD3 genomes AF: 0.276 AC: 41972 AN: 151890 Hom.: 7551 Cov.: 32

Gnomad AFR AF: 0.514

Gnomad AMI AF: 0.144

Gnomad AMR AF: 0.154

Gnomad ASJ AF: 0.184

Gnomad EAS AF: 0.133

Gnomad SAS AF: 0.199

Gnomad FIN AF: 0.241

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.189

Gnomad OTH AF: 0.250

GnomAD4 exome AF: 0.183 AC: 34866 AN: 190074 Hom.: 3728 Cov.: 0 AF XY: 0.182 AC XY: 18197 AN XY: 99728

Gnomad4 AFR exome AF: 0.503

Gnomad4 AMR exome AF: 0.126

Gnomad4 ASJ exome AF: 0.176

Gnomad4 EAS exome AF: 0.106

Gnomad4 SAS exome AF: 0.188

Gnomad4 FIN exome AF: 0.212

Gnomad4 NFE exome AF: 0.178

Gnomad4 OTH exome AF: 0.194

GnomAD4 genome AF: 0.276 AC: 42027 AN: 152008 Hom.: 7567 Cov.: 32 AF XY: 0.274 AC XY: 20348 AN XY: 74296

Gnomad4 AFR AF: 0.514

Gnomad4 AMR AF: 0.154

Gnomad4 ASJ AF: 0.184

Gnomad4 EAS AF: 0.132

Gnomad4 SAS AF: 0.199

Gnomad4 FIN AF: 0.241

Gnomad4 NFE AF: 0.189

Gnomad4 OTH AF: 0.252

Alfa AF: 0.218 Hom.: 924

Bravo AF: 0.281

Asia WGS AF: 0.208 AC: 722 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	11
DANN	Benign	0.82
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3

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: rs2287067; hg19: chr7-12370533;