7-12330907-T-C

Variant names:

• chr7-12330907-T-C
• rs2287067
• NM_001135924.3:c.*276A>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.*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
• Publications: 4 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=-0.76).
• 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 rank	MANE	Protein	UniProt
VWDE	NM_001135924.3	c.*276A>G		3_prime_UTR_variant	Exon 29 of 29	ENST00000275358.8	NP_001129396.1
VWDE	NR_144534.2	n.5871A>G		non_coding_transcript_exon_variant	Exon 30 of 30
VWDE	NM_001346972.2	c.*276A>G		3_prime_UTR_variant	Exon 27 of 27		NP_001333901.1
VWDE	NM_001346973.2	c.*276A>G		3_prime_UTR_variant	Exon 27 of 27		NP_001333902.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VWDE	ENST00000275358.8	c.*276A>G		3_prime_UTR_variant	Exon 29 of 29	5	NM_001135924.3	ENSP00000275358.3
VWDE	ENST00000485526.1	n.553A>G		non_coding_transcript_exon_variant	Exon 2 of 2	2
VWDE	ENST00000452576.6	n.*1813A>G		downstream_gene_variant		1		ENSP00000401687.2
VWDE	ENST00000521169.5	n.*3427A>G		downstream_gene_variant		5		ENSP00000428810.1

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

African (AFR) AF: 0.503 AC: 2350 AN: 4672

American (AMR) AF: 0.126 AC: 706 AN: 5586

Ashkenazi Jewish (ASJ) AF: 0.176 AC: 1105 AN: 6284

East Asian (EAS) AF: 0.106 AC: 1317 AN: 12442

South Asian (SAS) AF: 0.188 AC: 3383 AN: 17968

European-Finnish (FIN) AF: 0.212 AC: 2392 AN: 11298

Middle Eastern (MID) AF: 0.173 AC: 159 AN: 920

European-Non Finnish (NFE) AF: 0.178 AC: 21215 AN: 119386

Other (OTH) AF: 0.194 AC: 2239 AN: 11518

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

African (AFR) AF: 0.514 AC: 21308 AN: 41450

American (AMR) AF: 0.154 AC: 2348 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.184 AC: 637 AN: 3466

East Asian (EAS) AF: 0.132 AC: 682 AN: 5160

South Asian (SAS) AF: 0.199 AC: 958 AN: 4824

European-Finnish (FIN) AF: 0.241 AC: 2542 AN: 10564

Middle Eastern (MID) AF: 0.224 AC: 66 AN: 294

European-Non Finnish (NFE) AF: 0.189 AC: 12823 AN: 67968

Other (OTH) AF: 0.252 AC: 532 AN: 2110

Alfa AF: 0.225 Hom.: 1017

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
PhyloP100		0.053
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3
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: rs2287067; hg19: chr7-12370533;