NM_001130142.2:c.931-65T>C

Variant names:

• chr11-124123301-T-C
• rs880321
• NM_001130142.2:c.931-65T>C

Variant summary

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

The NM_001130142.2(VWA5A):​c.931-65T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.1 in 1,541,612 control chromosomes in the GnomAD database, including 8,421 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 0.083 (608 hom., cov: 32)
  • Exomes 𝑓: 0.10 (7813 hom.)
• Consequence: VWA5A NM_001130142.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.582
• Publications: 6 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=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.107 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001130142.2. 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.931-65T>C		intron	N/A	NP_001123614.1
	VWA5A	NM_014622.5		c.931-65T>C		intron	N/A	NP_055437.2
	VWA5A	NM_198315.3		c.931-65T>C		intron	N/A	NP_938057.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VWA5A	ENST00000456829.7	TSL:1 MANE Select	c.931-65T>C		intron	N/A	ENSP00000407726.2
	VWA5A	ENST00000392748.5	TSL:1	c.931-65T>C		intron	N/A	ENSP00000376504.1
	VWA5A	ENST00000361352.9	TSL:1	c.931-65T>C		intron	N/A	ENSP00000355070.5

Frequencies

GnomAD3 genomes AF: 0.0828 AC: 12581 AN: 152036 Hom.: 610 Cov.: 32

Gnomad AFR AF: 0.0497

Gnomad AMI AF: 0.0340

Gnomad AMR AF: 0.0655

Gnomad ASJ AF: 0.0613

Gnomad EAS AF: 0.0358

Gnomad SAS AF: 0.104

Gnomad FIN AF: 0.0917

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.109

Gnomad OTH AF: 0.0866

GnomAD4 exome AF: 0.102 AC: 142045 AN: 1389458 Hom.: 7813 Cov.: 23 AF XY: 0.102 AC XY: 70947 AN XY: 693076

African (AFR) AF: 0.0461 AC: 1432 AN: 31062

American (AMR) AF: 0.0534 AC: 2070 AN: 38736

Ashkenazi Jewish (ASJ) AF: 0.0525 AC: 1289 AN: 24556

East Asian (EAS) AF: 0.0536 AC: 2111 AN: 39380

South Asian (SAS) AF: 0.0989 AC: 8005 AN: 80900

European-Finnish (FIN) AF: 0.102 AC: 5296 AN: 51712

Middle Eastern (MID) AF: 0.0577 AC: 321 AN: 5562

European-Non Finnish (NFE) AF: 0.110 AC: 116099 AN: 1059830

Other (OTH) AF: 0.0939 AC: 5422 AN: 57720

GnomAD4 genome AF: 0.0827 AC: 12582 AN: 152154 Hom.: 608 Cov.: 32 AF XY: 0.0801 AC XY: 5956 AN XY: 74390

African (AFR) AF: 0.0497 AC: 2063 AN: 41526

American (AMR) AF: 0.0654 AC: 1000 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0613 AC: 213 AN: 3472

East Asian (EAS) AF: 0.0359 AC: 185 AN: 5152

South Asian (SAS) AF: 0.104 AC: 499 AN: 4812

European-Finnish (FIN) AF: 0.0917 AC: 971 AN: 10590

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.109 AC: 7424 AN: 67990

Other (OTH) AF: 0.0857 AC: 181 AN: 2112

Alfa AF: 0.101 Hom.: 1509

Bravo AF: 0.0787

Asia WGS AF: 0.0710 AC: 249 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	6.0
DANN	Benign	0.53
PhyloP100		0.58
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: rs880321; hg19: chr11-123994008;