Variant 10-29458386-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000355867.9(SVIL):c.6558+48G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.151 in 1,610,188 control chromosomes in the GnomAD database, including 19,738 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.14 ( 1683 hom., cov: 33)

Exomes 𝑓: 0.15 ( 18055 hom. )

Consequence

SVIL
ENST00000355867.9 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.57

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 10-29458386-C-T is Benign according to our data. Variant chr10-29458386-C-T is described in ClinVar as [Benign]. Clinvar id is 1228692.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.287 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.6558+48G>A		intron_variant		ENST00000355867.9	NP_068506.2
SVIL-AS1	NR_110927.1 linkuse as main transcript	n.182-28769C>T		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.6558+48G>A		intron_variant		1	NM_021738.3	ENSP00000348128	A2	O95425-1
SVIL-AS1	ENST00000684815.1 linkuse as main transcript	n.236+42974C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.142

AC:

21610

AN:

152018

Hom.:

1677

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0993

Gnomad AMI

AF:

0.0581

Gnomad AMR

AF:

0.163

Gnomad ASJ

AF:

0.106

Gnomad EAS

AF:

0.299

Gnomad SAS

AF:

0.180

Gnomad FIN

AF:

0.196

Gnomad MID

AF:

0.139

Gnomad NFE

AF:

0.144

Gnomad OTH

AF:

0.137

GnomAD3 exomes

AF:

0.163

AC:

39586

AN:

242912

Hom.:

3426

AF XY:

0.163

AC XY:

21339

AN XY:

131140

show subpopulations

Gnomad AFR exome

AF:

0.0988

Gnomad AMR exome

AF:

0.210

Gnomad ASJ exome

AF:

0.0972

Gnomad EAS exome

AF:

0.298

Gnomad SAS exome

AF:

0.170

Gnomad FIN exome

AF:

0.200

Gnomad NFE exome

AF:

0.134

Gnomad OTH exome

AF:

0.155

GnomAD4 exome

AF:

0.152

AC:

221584

AN:

1458052

Hom.:

18055

Cov.:

AF XY:

0.153

AC XY:

110974

AN XY:

725138

show subpopulations

Gnomad4 AFR exome

AF:

0.0966

Gnomad4 AMR exome

AF:

0.216

Gnomad4 ASJ exome

AF:

0.108

Gnomad4 EAS exome

AF:

0.312

Gnomad4 SAS exome

AF:

0.184

Gnomad4 FIN exome

AF:

0.203

Gnomad4 NFE exome

AF:

0.142

Gnomad4 OTH exome

AF:

0.152

GnomAD4 genome

AF:

0.142

AC:

21628

AN:

152136

Hom.:

1683

Cov.:

AF XY:

0.146

AC XY:

10868

AN XY:

74362

show subpopulations

Gnomad4 AFR

AF:

0.0993

Gnomad4 AMR

AF:

0.164

Gnomad4 ASJ

AF:

0.106

Gnomad4 EAS

AF:

0.299

Gnomad4 SAS

AF:

0.179

Gnomad4 FIN

AF:

0.196

Gnomad4 NFE

AF:

0.144

Gnomad4 OTH

AF:

0.135

Alfa

AF:

0.0945

Hom.:

165

Bravo

AF:

0.139

Asia WGS

AF:

0.229

AC:

793

AN:

3478

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	clinical testing	GeneDx	May 16, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.043

DANN

Benign

0.76

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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