rs4936894

Variant names:

• chr11-124146786-G-A
• rs4936894
• NM_001130142.2:c.*841G>A

Variant summary

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

The ENST00000456829.7(VWA5A):​c.*841G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.188 in 152,364 control chromosomes in the GnomAD database, including 3,265 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 0.19 (3256 hom., cov: 31)
  • Exomes 𝑓: 0.24 (9 hom.)
• Consequence: VWA5A ENST00000456829.7 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.54
• Publications: 16 publications found

Genes affected

VWA5A (HGNC:6658): (von Willebrand factor A domain containing 5A) Located in nucleoplasm. [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=-1.02).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.448 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000456829.7. 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
	VWA5A	NM_001130142.2	MANE Select	c.*841G>A		3_prime_UTR	Exon 19 of 19	NP_001123614.1
	VWA5A	NM_014622.5		c.*841G>A		3_prime_UTR	Exon 18 of 18	NP_055437.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VWA5A	ENST00000456829.7	TSL:1 MANE Select	c.*841G>A		3_prime_UTR	Exon 19 of 19	ENSP00000407726.2
	VWA5A	ENST00000392748.5	TSL:1	c.*841G>A		3_prime_UTR	Exon 18 of 18	ENSP00000376504.1

Frequencies

GnomAD3 genomes AF: 0.188 AC: 28502 AN: 151922 Hom.: 3260 Cov.: 31

Gnomad AFR AF: 0.0707

Gnomad AMI AF: 0.130

Gnomad AMR AF: 0.259

Gnomad ASJ AF: 0.218

Gnomad EAS AF: 0.463

Gnomad SAS AF: 0.142

Gnomad FIN AF: 0.202

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.222

Gnomad OTH AF: 0.188

GnomAD4 exome AF: 0.238 AC: 77 AN: 324 Hom.: 9 Cov.: 0 AF XY: 0.235 AC XY: 38 AN XY: 162

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.247 AC: 71 AN: 288

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.167 AC: 5 AN: 30

Other (OTH) AF: 0.250 AC: 1 AN: 4

GnomAD4 genome AF: 0.188 AC: 28508 AN: 152040 Hom.: 3256 Cov.: 31 AF XY: 0.191 AC XY: 14194 AN XY: 74308

African (AFR) AF: 0.0707 AC: 2934 AN: 41480

American (AMR) AF: 0.259 AC: 3947 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.218 AC: 754 AN: 3464

East Asian (EAS) AF: 0.464 AC: 2388 AN: 5152

South Asian (SAS) AF: 0.143 AC: 689 AN: 4816

European-Finnish (FIN) AF: 0.202 AC: 2137 AN: 10580

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.222 AC: 15110 AN: 67960

Other (OTH) AF: 0.188 AC: 398 AN: 2114

Alfa AF: 0.209 Hom.: 12424

Bravo AF: 0.186

Asia WGS AF: 0.238 AC: 828 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.046
DANN	Benign	0.47
PhyloP100		-3.5
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: rs4936894; hg19: chr11-124017493; COSMIC: COSV107469085;