Variant 10-29462163-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_021738.3(SVIL):c.6402+114C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.078 in 1,366,258 control chromosomes in the GnomAD database, including 4,374 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.087 ( 591 hom., cov: 33)

Exomes 𝑓: 0.077 ( 3783 hom. )

Consequence

SVIL
NM_021738.3 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.49

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

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

BP6

Variant 10-29462163-G-C is Benign according to our data. Variant chr10-29462163-G-C is described in ClinVar as [Benign]. Clinvar id is 1270993.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.12 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.6402+114C>G		intron_variant		ENST00000355867.9	NP_068506.2	O95425-1Q569J5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SVIL	ENST00000355867.9 linkuse as main transcript	c.6402+114C>G		intron_variant		1	NM_021738.3	ENSP00000348128.4		O95425-1

Frequencies

GnomAD3 genomes

AF:

0.0868

AC:

13194

AN:

152046

Hom.:

591

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0953

Gnomad AMI

AF:

0.0833

Gnomad AMR

AF:

0.124

Gnomad ASJ

AF:

0.0819

Gnomad EAS

AF:

0.0377

Gnomad SAS

AF:

0.0657

Gnomad FIN

AF:

0.0839

Gnomad MID

AF:

0.108

Gnomad NFE

AF:

0.0786

Gnomad OTH

AF:

0.101

GnomAD4 exome

AF:

0.0769

AC:

93358

AN:

1214094

Hom.:

3783

AF XY:

0.0764

AC XY:

45554

AN XY:

595902

show subpopulations

Gnomad4 AFR exome

AF:

0.0989

Gnomad4 AMR exome

AF:

0.133

Gnomad4 ASJ exome

AF:

0.0823

Gnomad4 EAS exome

AF:

0.0604

Gnomad4 SAS exome

AF:

0.0662

Gnomad4 FIN exome

AF:

0.0900

Gnomad4 NFE exome

AF:

0.0755

Gnomad4 OTH exome

AF:

0.0730

GnomAD4 genome

AF:

0.0868

AC:

13214

AN:

152164

Hom.:

591

Cov.:

AF XY:

0.0866

AC XY:

6441

AN XY:

74402

show subpopulations

Gnomad4 AFR

AF:

0.0955

Gnomad4 AMR

AF:

0.124

Gnomad4 ASJ

AF:

0.0819

Gnomad4 EAS

AF:

0.0374

Gnomad4 SAS

AF:

0.0664

Gnomad4 FIN

AF:

0.0839

Gnomad4 NFE

AF:

0.0786

Gnomad4 OTH

AF:

0.100

Alfa

AF:

0.0813

Hom.:

Bravo

AF:

0.0896

Asia WGS

AF:

0.0520

AC:

182

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

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

-0.90

CADD

Benign

DANN

Benign

0.73

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