Variant chr10-29458292-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The ENST00000355867.9(SVIL):c.6600C>T(p.Pro2200=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 1,613,960 control chromosomes in the GnomAD database, including 11,845 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.095 ( 869 hom., cov: 33)

Exomes 𝑓: 0.12 ( 10976 hom. )

Consequence

SVIL
ENST00000355867.9 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.23

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:51219): (SVIL antisense RNA 1)

SVIL-AS1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.76).

BP6

Variant 10-29458292-G-A is Benign according to our data. Variant chr10-29458292-G-A is described in ClinVar as [Benign]. Clinvar id is 1225817.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.23 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.13 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SVIL	NM_021738.3 linkuse as main transcript	c.6600C>T	p.Pro2200=	synonymous_variant	38/38	ENST00000355867.9	NP_068506.2
SVIL-AS1	NR_110927.1 linkuse as main transcript	n.182-28863G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SVIL	ENST00000355867.9 linkuse as main transcript	c.6600C>T	p.Pro2200=	synonymous_variant	38/38	1	NM_021738.3	ENSP00000348128	A2	O95425-1
SVIL-AS1	ENST00000684815.1 linkuse as main transcript	n.236+42880G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.0950

AC:

14441

AN:

152058

Hom.:

870

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0467

Gnomad AMI

AF:

0.163

Gnomad AMR

AF:

0.0849

Gnomad ASJ

AF:

0.0504

Gnomad EAS

AF:

0.000578

Gnomad SAS

AF:

0.0292

Gnomad FIN

AF:

0.146

Gnomad MID

AF:

0.0510

Gnomad NFE

AF:

0.132

Gnomad OTH

AF:

0.0875

GnomAD3 exomes

AF:

0.0889

AC:

22350

AN:

251368

Hom.:

1352

AF XY:

0.0885

AC XY:

12029

AN XY:

135858

show subpopulations

Gnomad AFR exome

AF:

0.0468

Gnomad AMR exome

AF:

0.0461

Gnomad ASJ exome

AF:

0.0555

Gnomad EAS exome

AF:

0.000217

Gnomad SAS exome

AF:

0.0319

Gnomad FIN exome

AF:

0.152

Gnomad NFE exome

AF:

0.128

Gnomad OTH exome

AF:

0.0925

GnomAD4 exome

AF:

0.116

AC:

169418

AN:

1461784

Hom.:

10976

Cov.:

AF XY:

0.113

AC XY:

82453

AN XY:

727200

show subpopulations

Gnomad4 AFR exome

AF:

0.0457

Gnomad4 AMR exome

AF:

0.0486

Gnomad4 ASJ exome

AF:

0.0548

Gnomad4 EAS exome

AF:

0.000252

Gnomad4 SAS exome

AF:

0.0317

Gnomad4 FIN exome

AF:

0.153

Gnomad4 NFE exome

AF:

0.132

Gnomad4 OTH exome

AF:

0.103

GnomAD4 genome

AF:

0.0949

AC:

14438

AN:

152176

Hom.:

869

Cov.:

AF XY:

0.0956

AC XY:

7109

AN XY:

74376

show subpopulations

Gnomad4 AFR

AF:

0.0466

Gnomad4 AMR

AF:

0.0848

Gnomad4 ASJ

AF:

0.0504

Gnomad4 EAS

AF:

0.000580

Gnomad4 SAS

AF:

0.0290

Gnomad4 FIN

AF:

0.146

Gnomad4 NFE

AF:

0.132

Gnomad4 OTH

AF:

0.0866

Alfa

AF:

0.111

Hom.:

532

Bravo

AF:

0.0881

Asia WGS

AF:

0.0190

AC:

AN:

3478

EpiCase

AF:

0.120

EpiControl

AF:

0.112

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 04, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

2.3

DANN

Benign

0.85

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over