Variant chr10-29471280-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 NM_021738.3(SVIL):c.5530-37G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.376 in 1,527,722 control chromosomes in the GnomAD database, including 109,941 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.39 ( 11732 hom., cov: 32)

Exomes 𝑓: 0.37 ( 98209 hom. )

Consequence

SVIL
NM_021738.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.86

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=-0.92).

BP6

Variant 10-29471280-C-T is Benign according to our data. Variant chr10-29471280-C-T is described in ClinVar as [Benign]. Clinvar id is 1222618.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.52 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SVIL	NM_021738.3 linkuse as main transcript	c.5530-37G>A		intron_variant		ENST00000355867.9
SVIL-AS1	NR_110927.1 linkuse as main transcript	n.182-15875C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SVIL	ENST00000355867.9 linkuse as main transcript	c.5530-37G>A		intron_variant		1	NM_021738.3	A2	O95425-1
SVIL-AS1	ENST00000684815.1 linkuse as main transcript	n.237-39148C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.388

AC:

58843

AN:

151784

Hom.:

11706

Cov.:

show subpopulations

Gnomad AFR

AF:

0.395

Gnomad AMI

AF:

0.249

Gnomad AMR

AF:

0.429

Gnomad ASJ

AF:

0.230

Gnomad EAS

AF:

0.536

Gnomad SAS

AF:

0.396

Gnomad FIN

AF:

0.484

Gnomad MID

AF:

0.304

Gnomad NFE

AF:

0.359

Gnomad OTH

AF:

0.352

GnomAD3 exomes

AF:

0.418

AC:

84331

AN:

201848

Hom.:

17600

AF XY:

0.412

AC XY:

45055

AN XY:

109352

show subpopulations

Gnomad AFR exome

AF:

0.409

Gnomad AMR exome

AF:

0.516

Gnomad ASJ exome

AF:

0.252

Gnomad EAS exome

AF:

0.555

Gnomad SAS exome

AF:

0.405

Gnomad FIN exome

AF:

0.495

Gnomad NFE exome

AF:

0.367

Gnomad OTH exome

AF:

0.394

GnomAD4 exome

AF:

0.375

AC:

515548

AN:

1375820

Hom.:

98209

Cov.:

AF XY:

0.375

AC XY:

254088

AN XY:

678420

show subpopulations

Gnomad4 AFR exome

AF:

0.389

Gnomad4 AMR exome

AF:

0.500

Gnomad4 ASJ exome

AF:

0.236

Gnomad4 EAS exome

AF:

0.533

Gnomad4 SAS exome

AF:

0.394

Gnomad4 FIN exome

AF:

0.482

Gnomad4 NFE exome

AF:

0.361

Gnomad4 OTH exome

AF:

0.373

GnomAD4 genome

AF:

0.388

AC:

58923

AN:

151902

Hom.:

11732

Cov.:

AF XY:

0.397

AC XY:

29497

AN XY:

74222

show subpopulations

Gnomad4 AFR

AF:

0.395

Gnomad4 AMR

AF:

0.430

Gnomad4 ASJ

AF:

0.230

Gnomad4 EAS

AF:

0.536

Gnomad4 SAS

AF:

0.396

Gnomad4 FIN

AF:

0.484

Gnomad4 NFE

AF:

0.359

Gnomad4 OTH

AF:

0.355

Alfa

AF:

0.359

Hom.:

2986

Bravo

AF:

0.386

Asia WGS

AF:

0.442

AC:

1534

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	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 15, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.30

DANN

Benign

0.50

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