dbSNP rs1886999: SVIL:c.6402+256T>C (chr10-29462021-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_021738.3(SVIL):c.6402+256T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.556 in 152,144 control chromosomes in the GnomAD database, including 25,073 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 0.56 ( 25073 hom., cov: 33)

Consequence

SVIL
NM_021738.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.28

Publications

0 publications found

Variant links:

Genes affected

SVIL (HGNC:11480): (supervillin) This gene encodes a bipartite protein with distinct amino- and carboxy-terminal domains. The amino-terminus contains nuclear localization signals and the carboxy-terminus contains numerous consecutive sequences with extensive similarity to proteins in the gelsolin family of actin-binding proteins, which cap, nucleate, and/or sever actin filaments. The gene product is tightly associated with both actin filaments and plasma membranes, suggesting a role as a high-affinity link between the actin cytoskeleton and the membrane. The encoded protein appears to aid in both myosin II assembly during cell spreading and disassembly of focal adhesions. Several transcript variants encoding different isoforms of supervillin have been described. [provided by RefSeq, Apr 2016]

SVIL links:

SVIL-AS1 (HGNC:):

SVIL-AS1 links:

SVIL-AS1 (HGNC:51219): (SVIL antisense RNA 1)

SVIL-AS1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.748 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021738.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SVIL	NM_021738.3	MANE Select	c.6402+256T>C	intron	N/A	NP_068506.2	O95425-1
SVIL	NM_001323599.2		c.5472+256T>C	intron	N/A	NP_001310528.1	A0A6I8PIX7
SVIL	NM_001323600.1		c.5220+256T>C	intron	N/A	NP_001310529.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SVIL	ENST00000355867.9	TSL:1 MANE Select	c.6402+256T>C	intron	N/A	ENSP00000348128.4	O95425-1
SVIL	ENST00000375400.7	TSL:1	c.5124+256T>C	intron	N/A	ENSP00000364549.3	O95425-2
SVIL-AS1	ENST00000413405.7	TSL:1	n.212-25134A>G	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.556

AC:

84478

AN:

152026

Hom.:

25022

Cov.:

show subpopulations

Gnomad AFR

AF:

0.755

Gnomad AMI

AF:

0.334

Gnomad AMR

AF:

0.585

Gnomad ASJ

AF:

0.319

Gnomad EAS

AF:

0.579

Gnomad SAS

AF:

0.561

Gnomad FIN

AF:

0.569

Gnomad MID

AF:

0.459

Gnomad NFE

AF:

0.440

Gnomad OTH

AF:

0.511

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.556

AC:

84597

AN:

152144

Hom.:

25073

Cov.:

AF XY:

0.563

AC XY:

41897

AN XY:

74386

show subpopulations

African (AFR)

AF:

0.755

AC:

31358

AN:

41520

American (AMR)

AF:

0.586

AC:

8951

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.319

AC:

1108

AN:

3468

East Asian (EAS)

AF:

0.579

AC:

3004

AN:

5188

South Asian (SAS)

AF:

0.560

AC:

2706

AN:

4830

European-Finnish (FIN)

AF:

0.569

AC:

6015

AN:

10576

Middle Eastern (MID)

AF:

0.463

AC:

136

AN:

294

European-Non Finnish (NFE)

AF:

0.440

AC:

29931

AN:

67962

Other (OTH)

AF:

0.514

AC:

1084

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1823

3646

5470

7293

9116

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

718

1436

2154

2872

3590

<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:

0.523

Hom.:

2832

Bravo

AF:

0.565

Asia WGS

AF:

0.557

AC:

1935

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.21

(source)

DANN

Benign

0.28

PhyloP100

-1.3

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over