6-31774290-A-G

Position:

• chr6-31774290-A-G

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VWA7	NM_025258.3	c.721+226T>C		intron_variant		ENST00000375688.5	NP_079534.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VWA7	ENST00000375688.5	c.721+226T>C		intron_variant		5	NM_025258.3	ENSP00000364840	P1
VWA7	ENST00000467576.1	n.700+226T>C		intron_variant, non_coding_transcript_variant		2

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

Gnomad4 AFR AF: 0.702

Gnomad4 AMR AF: 0.437

Gnomad4 ASJ AF: 0.311

Gnomad4 EAS AF: 0.384

Gnomad4 SAS AF: 0.429

Gnomad4 FIN AF: 0.450

Gnomad4 NFE AF: 0.332

Gnomad4 OTH AF: 0.455

Alfa AF: 0.384 Hom.: 4251

Bravo AF: 0.466

Asia WGS AF: 0.512 AC: 1778 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	6.1
DANN	Benign	0.79

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

Publications

LitVar

Other links and lift over

dbSNP: rs707929; hg19: chr6-31742067;