rs6481619

Positions:

• chr10-29694025-A-C
• chr10-29694025-A-G

Variant summary

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

The NM_001323599.2(SVIL):​c.-399-7374T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.25 in 151,808 control chromosomes in the GnomAD database, including 4,849 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 0.25 (4849 hom., cov: 30)
• Consequence: SVIL NM_001323599.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.427

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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.357 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SVIL	NM_001323599.2	c.-399-7374T>G		intron_variant			NP_001310528.1
SVIL	NM_001323600.1	c.-399-7374T>G		intron_variant			NP_001310529.1
SVIL	NM_003174.3	c.-399-7374T>G		intron_variant			NP_003165.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SVIL	ENST00000375400.7	c.-399-7374T>G		intron_variant		1		ENSP00000364549.3
SVIL	ENST00000674475.1	c.-399-7374T>G		intron_variant				ENSP00000501521.1
SVIL	ENST00000674490.1	c.-399-7374T>G		intron_variant				ENSP00000501398.1

Frequencies

GnomAD3 genomes AF: 0.250 AC: 37851 AN: 151690 Hom.: 4846 Cov.: 30

Gnomad AFR AF: 0.201

Gnomad AMI AF: 0.136

Gnomad AMR AF: 0.239

Gnomad ASJ AF: 0.209

Gnomad EAS AF: 0.370

Gnomad SAS AF: 0.221

Gnomad FIN AF: 0.284

Gnomad MID AF: 0.287

Gnomad NFE AF: 0.273

Gnomad OTH AF: 0.240

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.250 AC: 37880 AN: 151808 Hom.: 4849 Cov.: 30 AF XY: 0.254 AC XY: 18825 AN XY: 74162

Gnomad4 AFR AF: 0.201

Gnomad4 AMR AF: 0.238

Gnomad4 ASJ AF: 0.209

Gnomad4 EAS AF: 0.371

Gnomad4 SAS AF: 0.222

Gnomad4 FIN AF: 0.284

Gnomad4 NFE AF: 0.273

Gnomad4 OTH AF: 0.242

Alfa AF: 0.264 Hom.: 9128

Bravo AF: 0.248

Asia WGS AF: 0.293 AC: 1021 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.6
DANN	Benign	0.69

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs6481619; hg19: chr10-29982954;