rs1270874

Variant names:

• chr10-29550935-A-C
• rs1270874
• NM_021738.3:c.489T>G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_021738.3(SVIL):​c.489T>G​(p.Ala163Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.734 in 1,613,692 control chromosomes in the GnomAD database, including 436,481 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.72 (39029 hom., cov: 30)
  • Exomes 𝑓: 0.74 (397452 hom.)
• Consequence: SVIL NM_021738.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.58

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]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP7: Synonymous conserved (PhyloP=-1.58 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.815 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SVIL	NM_021738.3	c.489T>G	p.Ala163Ala	synonymous_variant	Exon 6 of 38	ENST00000355867.9	NP_068506.2
SVIL	NM_001323599.2	c.489T>G	p.Ala163Ala	synonymous_variant	Exon 8 of 39		NP_001310528.1
SVIL	NM_001323600.1	c.489T>G	p.Ala163Ala	synonymous_variant	Exon 8 of 37		NP_001310529.1
SVIL	NM_003174.3	c.489T>G	p.Ala163Ala	synonymous_variant	Exon 8 of 36		NP_003165.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SVIL	ENST00000355867.9	c.489T>G	p.Ala163Ala	synonymous_variant	Exon 6 of 38	1	NM_021738.3	ENSP00000348128.4
SVIL	ENST00000375400.7	c.489T>G	p.Ala163Ala	synonymous_variant	Exon 8 of 36	1		ENSP00000364549.3
SVIL	ENST00000375398.6	c.489T>G	p.Ala163Ala	synonymous_variant	Exon 6 of 37	5		ENSP00000364547.3
SVIL	ENST00000674475.1	c.489T>G	p.Ala163Ala	synonymous_variant	Exon 8 of 39			ENSP00000501521.1

Frequencies

GnomAD3 genomes AF: 0.716 AC: 108620 AN: 151696 Hom.: 38986 Cov.: 30

Gnomad AFR AF: 0.662

Gnomad AMI AF: 0.774

Gnomad AMR AF: 0.719

Gnomad ASJ AF: 0.617

Gnomad EAS AF: 0.836

Gnomad SAS AF: 0.765

Gnomad FIN AF: 0.776

Gnomad MID AF: 0.634

Gnomad NFE AF: 0.731

Gnomad OTH AF: 0.696

GnomAD3 exomes AF: 0.735 AC: 184795 AN: 251448 Hom.: 68152 AF XY: 0.735 AC XY: 99909 AN XY: 135900

Gnomad AFR exome AF: 0.659

Gnomad AMR exome AF: 0.722

Gnomad ASJ exome AF: 0.616

Gnomad EAS exome AF: 0.830

Gnomad SAS exome AF: 0.768

Gnomad FIN exome AF: 0.775

Gnomad NFE exome AF: 0.730

Gnomad OTH exome AF: 0.709

GnomAD4 exome AF: 0.736 AC: 1076298 AN: 1461878 Hom.: 397452 Cov.: 86 AF XY: 0.737 AC XY: 535948 AN XY: 727238

Gnomad4 AFR exome AF: 0.656

Gnomad4 AMR exome AF: 0.718

Gnomad4 ASJ exome AF: 0.620

Gnomad4 EAS exome AF: 0.848

Gnomad4 SAS exome AF: 0.766

Gnomad4 FIN exome AF: 0.776

Gnomad4 NFE exome AF: 0.735

Gnomad4 OTH exome AF: 0.719

GnomAD4 genome AF: 0.716 AC: 108722 AN: 151814 Hom.: 39029 Cov.: 30 AF XY: 0.720 AC XY: 53359 AN XY: 74154

Gnomad4 AFR AF: 0.663

Gnomad4 AMR AF: 0.720

Gnomad4 ASJ AF: 0.617

Gnomad4 EAS AF: 0.836

Gnomad4 SAS AF: 0.766

Gnomad4 FIN AF: 0.776

Gnomad4 NFE AF: 0.731

Gnomad4 OTH AF: 0.698

Alfa AF: 0.725 Hom.: 85918

Bravo AF: 0.709

Asia WGS AF: 0.784 AC: 2724 AN: 3478

EpiCase AF: 0.723

EpiControl AF: 0.716

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.44
DANN	Benign	0.37

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

Other links and lift over

dbSNP: rs1270874; hg19: chr10-29839864; COSMIC: COSV63446677; COSMIC: COSV63446677;