1-20314497-C-G

Variant names:

• chr1-20314497-C-G
• rs562282893
• NM_001039500.3:c.468C>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001039500.3(VWA5B1):​c.468C>G​(p.Ser156Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000214 in 1,399,474 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: VWA5B1 NM_001039500.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.326
• Publications: 0 publications found

Genes affected

VWA5B1 (HGNC:26538): (von Willebrand factor A domain containing 5B1) Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000226664 (HGNC:41146):

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2801593).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001039500.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VWA5B1	NM_001039500.3	MANE Select	c.468C>G	p.Ser156Arg	missense	Exon 4 of 22	NP_001034589.2	Q5TIE3-2
	VWA5B1	NM_001377531.1		c.153C>G	p.Ser51Arg	missense	Exon 4 of 22	NP_001364460.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VWA5B1	ENST00000289815.13	TSL:5 MANE Select	c.468C>G	p.Ser156Arg	missense	Exon 4 of 22	ENSP00000289815.9	Q5TIE3-2
	VWA5B1	ENST00000919186.1		c.468C>G	p.Ser156Arg	missense	Exon 4 of 22	ENSP00000589245.1
	VWA5B1	ENST00000375079.6	TSL:5	c.468C>G	p.Ser156Arg	missense	Exon 4 of 22	ENSP00000364220.1	Q5TIE3-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000214 AC: 3 AN: 1399474 Hom.: 0 Cov.: 32 AF XY: 0.00000290 AC XY: 2 AN XY: 690256

African (AFR) AF: 0.00 AC: 0 AN: 31598

American (AMR) AF: 0.00 AC: 0 AN: 35704

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25182

East Asian (EAS) AF: 0.00 AC: 0 AN: 35738

South Asian (SAS) AF: 0.0000379 AC: 3 AN: 79236

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49298

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5702

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1078988

Other (OTH) AF: 0.00 AC: 0 AN: 58028

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.62
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	18
DANN	Benign	0.95
DEOGEN2	Benign	0.011	T
Eigen	Benign	0.088
Eigen_PC	Benign	-0.013
FATHMM_MKL	Benign	0.71	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.037	D
MetaRNN	Benign	0.28	T
MetaSVM	Benign	-1.2	T
MutationAssessor	Uncertain	2.8	M
PhyloP100		-0.33
PrimateAI	Uncertain	0.52	T
PROVEAN	Uncertain	-2.8	D
REVEL	Benign	0.16
Sift	Uncertain	0.027	D
Sift4G	Uncertain	0.010	D
Polyphen		0.99	D
Vest4		0.42
MutPred		0.42		Gain of solvent accessibility (P = 4e-04)
MVP		0.13
ClinPred		0.97	D
GERP RS		0.80
Varity_R		0.36
gMVP		0.42
Mutation Taster		=67/33	polymorphism

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: rs562282893; hg19: chr1-20640990;