rs6809649

Variant names:

• chr3-37997491-T-C
• rs6809649
• NM_015873.4:c.570T>C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_015873.4(VILL):​c.570T>C​(p.Ala190Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.186 in 1,613,510 control chromosomes in the GnomAD database, including 31,069 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 0.23 (4955 hom., cov: 33)
  • Exomes 𝑓: 0.18 (26114 hom.)
• Consequence: VILL NM_015873.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.372
• Publications: 22 publications found

Genes affected

VILL (HGNC:30906): (villin like) The protein encoded by this gene belongs to the villin/gelsolin family. It contains 6 gelsolin-like repeats and a headpiece domain. It may play a role in actin-bundling. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP7: Synonymous conserved (PhyloP=0.372 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.399 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VILL	NM_015873.4	c.570T>C	p.Ala190Ala	synonymous_variant	Exon 7 of 20	ENST00000383759.7	NP_056957.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VILL	ENST00000383759.7	c.570T>C	p.Ala190Ala	synonymous_variant	Exon 7 of 20	5	NM_015873.4	ENSP00000373266.2
VILL	ENST00000283713.10	c.570T>C	p.Ala190Ala	synonymous_variant	Exon 7 of 20	1		ENSP00000283713.6
VILL	ENST00000484717.5	n.543T>C		non_coding_transcript_exon_variant	Exon 4 of 10	1
VILL	ENST00000465644.5	c.115-1439T>C		intron_variant	Intron 1 of 11	5		ENSP00000422096.1

Frequencies

GnomAD3 genomes AF: 0.229 AC: 34796 AN: 152020 Hom.: 4939 Cov.: 33

Gnomad AFR AF: 0.403

Gnomad AMI AF: 0.123

Gnomad AMR AF: 0.133

Gnomad ASJ AF: 0.110

Gnomad EAS AF: 0.0866

Gnomad SAS AF: 0.268

Gnomad FIN AF: 0.124

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.178

Gnomad OTH AF: 0.193

GnomAD2 exomes AF: 0.174 AC: 43555 AN: 250424 AF XY: 0.178

Gnomad AFR exome AF: 0.408

Gnomad AMR exome AF: 0.0834

Gnomad ASJ exome AF: 0.103

Gnomad EAS exome AF: 0.0835

Gnomad FIN exome AF: 0.129

Gnomad NFE exome AF: 0.173

Gnomad OTH exome AF: 0.161

GnomAD4 exome AF: 0.181 AC: 265123 AN: 1461372 Hom.: 26114 Cov.: 39 AF XY: 0.184 AC XY: 133565 AN XY: 726998

African (AFR) AF: 0.415 AC: 13886 AN: 33472

American (AMR) AF: 0.0911 AC: 4072 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.106 AC: 2780 AN: 26134

East Asian (EAS) AF: 0.0673 AC: 2672 AN: 39700

South Asian (SAS) AF: 0.263 AC: 22700 AN: 86246

European-Finnish (FIN) AF: 0.132 AC: 7008 AN: 53134

Middle Eastern (MID) AF: 0.181 AC: 1028 AN: 5688

European-Non Finnish (NFE) AF: 0.180 AC: 199754 AN: 1111910

Other (OTH) AF: 0.186 AC: 11223 AN: 60370

GnomAD4 genome AF: 0.229 AC: 34847 AN: 152138 Hom.: 4955 Cov.: 33 AF XY: 0.224 AC XY: 16694 AN XY: 74382

African (AFR) AF: 0.404 AC: 16752 AN: 41484

American (AMR) AF: 0.132 AC: 2022 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.110 AC: 381 AN: 3468

East Asian (EAS) AF: 0.0867 AC: 448 AN: 5170

South Asian (SAS) AF: 0.268 AC: 1292 AN: 4820

European-Finnish (FIN) AF: 0.124 AC: 1314 AN: 10610

Middle Eastern (MID) AF: 0.163 AC: 48 AN: 294

European-Non Finnish (NFE) AF: 0.178 AC: 12075 AN: 67986

Other (OTH) AF: 0.191 AC: 403 AN: 2110

Alfa AF: 0.192 Hom.: 11596

Bravo AF: 0.235

Asia WGS AF: 0.182 AC: 640 AN: 3478

EpiCase AF: 0.168

EpiControl AF: 0.168

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	8.3
DANN	Benign	0.40
PhyloP100		0.37
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs6809649; hg19: chr3-38038982; COSMIC: COSV52184723; COSMIC: COSV52184723;