rs6715989

Positions:

• chr2-98295808-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_144992.5(VWA3B):​c.3158-2099G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.283 in 152,134 control chromosomes in the GnomAD database, including 6,392 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 (6392 hom., cov: 33)
• Consequence: VWA3B NM_144992.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.692

Genes affected

VWA3B (HGNC:28385): (von Willebrand factor A domain containing 3B) This gene encodes an intracellular protein that contains a von Willebrand factor type A domain. Intracellular proteins with VWA domains are thought to function in transcription, DNA repair, ribosomal and membrane transport and the proteasome. Mutations in this gene are associated with Spinocerebellar ataxia, autosomal recessive 22. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, May 2017]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.354 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VWA3B	NM_144992.5	c.3158-2099G>A		intron_variant		ENST00000477737.6	NP_659429.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VWA3B	ENST00000477737.6	c.3158-2099G>A		intron_variant		1	NM_144992.5	ENSP00000417955	P1

Frequencies

GnomAD3 genomes AF: 0.283 AC: 43028 AN: 152016 Hom.: 6374 Cov.: 33

Gnomad AFR AF: 0.264

Gnomad AMI AF: 0.209

Gnomad AMR AF: 0.362

Gnomad ASJ AF: 0.276

Gnomad EAS AF: 0.216

Gnomad SAS AF: 0.187

Gnomad FIN AF: 0.164

Gnomad MID AF: 0.310

Gnomad NFE AF: 0.308

Gnomad OTH AF: 0.305

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

GnomAD4 genome AF: 0.283 AC: 43093 AN: 152134 Hom.: 6392 Cov.: 33 AF XY: 0.276 AC XY: 20566 AN XY: 74384

Gnomad4 AFR AF: 0.265

Gnomad4 AMR AF: 0.362

Gnomad4 ASJ AF: 0.276

Gnomad4 EAS AF: 0.217

Gnomad4 SAS AF: 0.189

Gnomad4 FIN AF: 0.164

Gnomad4 NFE AF: 0.308

Gnomad4 OTH AF: 0.302

Alfa AF: 0.309 Hom.: 9794

Bravo AF: 0.301

Asia WGS AF: 0.197 AC: 686 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.23
DANN	Benign	0.30

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: rs6715989; hg19: chr2-98912271;