Variant rs17756919 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_021738.3(SVIL):c.1851G>A(p.Val617=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.379 in 1,613,406 control chromosomes in the GnomAD database, including 119,486 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.37 ( 10590 hom., cov: 33)

Exomes 𝑓: 0.38 ( 108896 hom. )

Consequence

SVIL
NM_021738.3 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.31

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 -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.51).

BP6

Variant 10-29532160-C-T is Benign according to our data. Variant chr10-29532160-C-T is described in ClinVar as [Benign]. Clinvar id is 1235948.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=1.31 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.401 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
SVIL	NM_021738.3 linkuse as main transcript	c.1851G>A	p.Val617=	synonymous_variant	9/38	ENST00000355867.9
SVIL	NM_001323599.2 linkuse as main transcript	c.921G>A	p.Val307=	synonymous_variant	10/39
SVIL	NM_001323600.1 linkuse as main transcript	c.828-872G>A		intron_variant
SVIL	NM_003174.3 linkuse as main transcript	c.828-872G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SVIL	ENST00000355867.9 linkuse as main transcript	c.1851G>A	p.Val617=	synonymous_variant	9/38	1	NM_021738.3	A2	O95425-1
SVIL	ENST00000375400.7 linkuse as main transcript	c.828-872G>A		intron_variant		1		P2	O95425-2
SVIL	ENST00000375398.6 linkuse as main transcript	c.1851G>A	p.Val617=	synonymous_variant	9/37	5		A2	O95425-4
SVIL	ENST00000674475.1 linkuse as main transcript	c.921G>A	p.Val307=	synonymous_variant	10/39			A2

Frequencies

GnomAD3 genomes

AF:

0.368

AC:

55868

AN:

151976

Hom.:

10587

Cov.:

show subpopulations

Gnomad AFR

AF:

0.341

Gnomad AMI

AF:

0.656

Gnomad AMR

AF:

0.349

Gnomad ASJ

AF:

0.321

Gnomad EAS

AF:

0.0806

Gnomad SAS

AF:

0.301

Gnomad FIN

AF:

0.415

Gnomad MID

AF:

0.345

Gnomad NFE

AF:

0.405

Gnomad OTH

AF:

0.374

GnomAD3 exomes

AF:

0.346

AC:

86665

AN:

250812

Hom.:

16144

AF XY:

0.347

AC XY:

47044

AN XY:

135540

show subpopulations

Gnomad AFR exome

AF:

0.341

Gnomad AMR exome

AF:

0.270

Gnomad ASJ exome

AF:

0.323

Gnomad EAS exome

AF:

0.0848

Gnomad SAS exome

AF:

0.310

Gnomad FIN exome

AF:

0.422

Gnomad NFE exome

AF:

0.407

Gnomad OTH exome

AF:

0.368

GnomAD4 exome

AF:

0.381

AC:

556056

AN:

1461312

Hom.:

108896

Cov.:

AF XY:

0.379

AC XY:

275469

AN XY:

726972

show subpopulations

Gnomad4 AFR exome

AF:

0.341

Gnomad4 AMR exome

AF:

0.281

Gnomad4 ASJ exome

AF:

0.319

Gnomad4 EAS exome

AF:

0.0789

Gnomad4 SAS exome

AF:

0.309

Gnomad4 FIN exome

AF:

0.421

Gnomad4 NFE exome

AF:

0.403

Gnomad4 OTH exome

AF:

0.357

GnomAD4 genome

AF:

0.367

AC:

55887

AN:

152094

Hom.:

10590

Cov.:

AF XY:

0.365

AC XY:

27157

AN XY:

74350

show subpopulations

Gnomad4 AFR

AF:

0.341

Gnomad4 AMR

AF:

0.349

Gnomad4 ASJ

AF:

0.321

Gnomad4 EAS

AF:

0.0810

Gnomad4 SAS

AF:

0.301

Gnomad4 FIN

AF:

0.415

Gnomad4 NFE

AF:

0.406

Gnomad4 OTH

AF:

0.370

Alfa

AF:

0.389

Hom.:

26185

Bravo

AF:

0.360

Asia WGS

AF:

0.197

AC:

689

AN:

3478

EpiCase

AF:

0.408

EpiControl

AF:

0.398

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

-0.51

CADD

Benign

3.8

DANN

Benign

0.59

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

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