6-31774290-A-G

Variant names:

• chr6-31774290-A-G
• rs707929
• NM_025258.3:c.721+226T>C

Variant summary

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

The NM_025258.3(VWA7):​c.721+226T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.457 in 151,750 control chromosomes in the GnomAD database, including 17,776 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 0.46 (17776 hom., cov: 30)
• Consequence: VWA7 NM_025258.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.203
• Publications: 22 publications found

Genes affected

VWA7 (HGNC:13939): (von Willebrand factor A domain containing 7) Predicted to be located in 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.695 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_025258.3. 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
	VWA7	NM_025258.3	MANE Select	c.721+226T>C		intron	N/A	NP_079534.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VWA7	ENST00000375688.5	TSL:5 MANE Select	c.721+226T>C		intron	N/A	ENSP00000364840.4
	VWA7	ENST00000467576.1	TSL:2	n.700+226T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.457 AC: 69327 AN: 151632 Hom.: 17739 Cov.: 30

Gnomad AFR AF: 0.701

Gnomad AMI AF: 0.263

Gnomad AMR AF: 0.437

Gnomad ASJ AF: 0.311

Gnomad EAS AF: 0.383

Gnomad SAS AF: 0.429

Gnomad FIN AF: 0.450

Gnomad MID AF: 0.421

Gnomad NFE AF: 0.332

Gnomad OTH AF: 0.452

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.457 AC: 69418 AN: 151750 Hom.: 17776 Cov.: 30 AF XY: 0.459 AC XY: 34060 AN XY: 74164

African (AFR) AF: 0.702 AC: 29008 AN: 41350

American (AMR) AF: 0.437 AC: 6664 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.311 AC: 1080 AN: 3468

East Asian (EAS) AF: 0.384 AC: 1979 AN: 5160

South Asian (SAS) AF: 0.429 AC: 2058 AN: 4802

European-Finnish (FIN) AF: 0.450 AC: 4740 AN: 10522

Middle Eastern (MID) AF: 0.422 AC: 124 AN: 294

European-Non Finnish (NFE) AF: 0.332 AC: 22567 AN: 67886

Other (OTH) AF: 0.455 AC: 959 AN: 2106

Alfa AF: 0.394 Hom.: 26275

Bravo AF: 0.466

Asia WGS AF: 0.512 AC: 1778 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	6.1
DANN	Benign	0.79
PhyloP100		0.20
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs707929; hg19: chr6-31742067;