rs1328327

chr10-29575441-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021738.3(SVIL):c.-200-6129G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.534 in 204,134 control chromosomes in the GnomAD database, including 29,911 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 0.55 (23330 hom., cov: 33)
  • Exomes 𝑓: 0.50 (6581 hom.)
• Consequence: SVIL NM_021738.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.310

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.683 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SVIL	NM_021738.3	c.-200-6129G>A		intron_variant		ENST00000355867.9
SVIL	NM_001323599.2	c.-200-6129G>A		intron_variant
SVIL	NM_001323600.1	c.-200-6129G>A		intron_variant
SVIL	NM_003174.3	c.-200-6129G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SVIL	ENST00000355867.9	c.-200-6129G>A		intron_variant		1	NM_021738.3	A2

Frequencies

GnomAD3 genomes AF: 0.546 AC: 82955 AN: 151968 Hom.: 23277 Cov.: 33

Gnomad AFR AF: 0.689

Gnomad AMI AF: 0.589

Gnomad AMR AF: 0.582

Gnomad ASJ AF: 0.335

Gnomad EAS AF: 0.486

Gnomad SAS AF: 0.514

Gnomad FIN AF: 0.496

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.477

Gnomad OTH AF: 0.516

GnomAD4 exome AF: 0.500 AC: 26033 AN: 52048 Hom.: 6581 AF XY: 0.489 AC XY: 14956 AN XY: 30564

Gnomad4 AFR exome AF: 0.707

Gnomad4 AMR exome AF: 0.630

Gnomad4 ASJ exome AF: 0.332

Gnomad4 EAS exome AF: 0.489

Gnomad4 SAS exome AF: 0.508

Gnomad4 FIN exome AF: 0.489

Gnomad4 NFE exome AF: 0.463

Gnomad4 OTH exome AF: 0.481

GnomAD4 genome AF: 0.546 AC: 83068 AN: 152086 Hom.: 23330 Cov.: 33 AF XY: 0.547 AC XY: 40671 AN XY: 74344

Gnomad4 AFR AF: 0.689

Gnomad4 AMR AF: 0.583

Gnomad4 ASJ AF: 0.335

Gnomad4 EAS AF: 0.487

Gnomad4 SAS AF: 0.513

Gnomad4 FIN AF: 0.496

Gnomad4 NFE AF: 0.477

Gnomad4 OTH AF: 0.519

Alfa AF: 0.488 Hom.: 18938

Bravo AF: 0.559

Asia WGS AF: 0.540 AC: 1876 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	3.1
Dann	Benign	0.60

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: rs1328327; hg19: chr10-29864370; COSMIC: COSV63439240; COSMIC: COSV63439240;