6-31766524-G-T

Variant names:

• chr6-31766524-G-T
• rs758285570
• NM_025258.3:c.2123C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_025258.3(VWA7):​c.2123C>A​(p.Ala708Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,457,242 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. A708V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: VWA7 NM_025258.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.95
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.028447509).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VWA7	NM_025258.3	c.2123C>A	p.Ala708Glu	missense_variant	Exon 14 of 17	ENST00000375688.5	NP_079534.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VWA7	ENST00000375688.5	c.2123C>A	p.Ala708Glu	missense_variant	Exon 14 of 17	5	NM_025258.3	ENSP00000364840.4
VWA7	ENST00000467576.1	n.1986C>A		non_coding_transcript_exon_variant	Exon 14 of 15	2
VWA7	ENST00000486423.5	n.553C>A		non_coding_transcript_exon_variant	Exon 4 of 5	5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1457242 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 724418

African (AFR) AF: 0.00 AC: 0 AN: 33410

American (AMR) AF: 0.00 AC: 0 AN: 44498

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26036

East Asian (EAS) AF: 0.00 AC: 0 AN: 39546

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86064

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51964

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1109810

Other (OTH) AF: 0.00 AC: 0 AN: 60154

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.0020
DANN	Benign	0.75
DEOGEN2	Benign	0.00012	T
Eigen	Benign	-2.2
Eigen_PC	Benign	-2.3
FATHMM_MKL	Benign	0.012	N
M_CAP	Benign	0.0014	T
MetaRNN	Benign	0.028	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.0	N
PhyloP100		-2.9
PrimateAI	Benign	0.32	T
PROVEAN	Benign	0.42	N
REVEL	Benign	0.025
Sift	Benign	0.84	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.077
MutPred		0.33		Loss of helix (P = 0.0444);
MVP		0.040
MPC		0.34
ClinPred		0.074	T
GERP RS		-10
Varity_R		0.045
gMVP		0.31
Mutation Taster		=99/1	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: rs758285570; hg19: chr6-31734301;