Genetic Variant VILL:p.Ala190Ala (chr3-37997491-T-C) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.372

Publications

22 publications found

Variant links:

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]

VILL links:

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ACMG classification

Classification was made for transcript

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 link	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
VILL	ENST00000383759.7 link	c.570T>C	p.Ala190Ala	synonymous_variant	Exon 7 of 20	5	NM_015873.4	ENSP00000373266.2
VILL	ENST00000283713.10 link	c.570T>C	p.Ala190Ala	synonymous_variant	Exon 7 of 20	1		ENSP00000283713.6
VILL	ENST00000484717.5 link	n.543T>C		non_coding_transcript_exon_variant	Exon 4 of 10	1
VILL	ENST00000465644.5 link	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.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.184

AC XY:

133565

AN XY:

726998

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

12017

24034

36052

48069

60086

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7172

14344

21516

28688

35860

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.229

AC:

34847

AN:

152138

Hom.:

4955

Cov.:

AF XY:

0.224

AC XY:

16694

AN XY:

74382

show subpopulations

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:

AN:

294

European-Non Finnish (NFE)

AF:

0.178

AC:

12075

AN:

67986

Other (OTH)

AF:

0.191

AC:

403

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1310

2620

3930

5240

6550

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

360

720

1080

1440

1800

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

(source)

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)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over