Variant rs1328323 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.1773A>G(p.Lys591=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.409 in 1,613,678 control chromosomes in the GnomAD database, including 139,033 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.39 ( 12024 hom., cov: 32)

Exomes 𝑓: 0.41 ( 127009 hom. )

Consequence

SVIL
ENST00000355867.9 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.04

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.53).

BP6

Variant 10-29532594-T-C is Benign according to our data. Variant chr10-29532594-T-C is described in ClinVar as [Benign]. Clinvar id is 1260962.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.04 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.435 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
SVIL	NM_021738.3 linkuse as main transcript	c.1773A>G	p.Lys591=	synonymous_variant	8/38	ENST00000355867.9	NP_068506.2
SVIL	NM_001323599.2 linkuse as main transcript	c.909-422A>G		intron_variant			NP_001310528.1
SVIL	NM_001323600.1 linkuse as main transcript	c.828-1306A>G		intron_variant			NP_001310529.1
SVIL	NM_003174.3 linkuse as main transcript	c.828-1306A>G		intron_variant			NP_003165.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SVIL	ENST00000355867.9 linkuse as main transcript	c.1773A>G	p.Lys591=	synonymous_variant	8/38	1	NM_021738.3	ENSP00000348128	A2	O95425-1
SVIL	ENST00000375400.7 linkuse as main transcript	c.828-1306A>G		intron_variant		1		ENSP00000364549	P2	O95425-2
SVIL	ENST00000375398.6 linkuse as main transcript	c.1773A>G	p.Lys591=	synonymous_variant	8/37	5		ENSP00000364547	A2	O95425-4
SVIL	ENST00000674475.1 linkuse as main transcript	c.909-422A>G		intron_variant				ENSP00000501521	A2

Frequencies

GnomAD3 genomes

AF:

0.390

AC:

59317

AN:

151916

Hom.:

12020

Cov.:

show subpopulations

Gnomad AFR

AF:

0.347

Gnomad AMI

AF:

0.736

Gnomad AMR

AF:

0.371

Gnomad ASJ

AF:

0.351

Gnomad EAS

AF:

0.0808

Gnomad SAS

AF:

0.310

Gnomad FIN

AF:

0.444

Gnomad MID

AF:

0.361

Gnomad NFE

AF:

0.439

Gnomad OTH

AF:

0.394

GnomAD3 exomes

AF:

0.370

AC:

92957

AN:

251182

Hom.:

18713

AF XY:

0.372

AC XY:

50496

AN XY:

135754

show subpopulations

Gnomad AFR exome

AF:

0.348

Gnomad AMR exome

AF:

0.282

Gnomad ASJ exome

AF:

0.356

Gnomad EAS exome

AF:

0.0847

Gnomad SAS exome

AF:

0.319

Gnomad FIN exome

AF:

0.454

Gnomad NFE exome

AF:

0.444

Gnomad OTH exome

AF:

0.394

GnomAD4 exome

AF:

0.410

AC:

599913

AN:

1461644

Hom.:

127009

Cov.:

AF XY:

0.409

AC XY:

297101

AN XY:

727090

show subpopulations

Gnomad4 AFR exome

AF:

0.346

Gnomad4 AMR exome

AF:

0.294

Gnomad4 ASJ exome

AF:

0.352

Gnomad4 EAS exome

AF:

0.0789

Gnomad4 SAS exome

AF:

0.319

Gnomad4 FIN exome

AF:

0.455

Gnomad4 NFE exome

AF:

0.437

Gnomad4 OTH exome

AF:

0.383

GnomAD4 genome

AF:

0.390

AC:

59338

AN:

152034

Hom.:

12024

Cov.:

AF XY:

0.387

AC XY:

28793

AN XY:

74308

show subpopulations

Gnomad4 AFR

AF:

0.347

Gnomad4 AMR

AF:

0.370

Gnomad4 ASJ

AF:

0.351

Gnomad4 EAS

AF:

0.0812

Gnomad4 SAS

AF:

0.310

Gnomad4 FIN

AF:

0.444

Gnomad4 NFE

AF:

0.439

Gnomad4 OTH

AF:

0.391

Alfa

AF:

0.413

Hom.:

9233

Bravo

AF:

0.382

Asia WGS

AF:

0.202

AC:

704

AN:

3478

EpiCase

AF:

0.441

EpiControl

AF:

0.432

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	Feb 07, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.53

CADD

Benign

8.8

DANN

Benign

0.62

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