10-29558518-C-G

Position:

• chr10-29558518-C-G

Variant summary

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

The NM_021738.3(SVIL):​c.-50-3410G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.3 in 151,842 control chromosomes in the GnomAD database, including 7,092 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 0.30 (7092 hom., cov: 32)
• Consequence: SVIL NM_021738.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.342

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.38 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SVIL	NM_021738.3	c.-50-3410G>C		intron_variant		ENST00000355867.9	NP_068506.2
SVIL	NM_001323599.2	c.-50-3410G>C		intron_variant			NP_001310528.1
SVIL	NM_001323600.1	c.-50-3410G>C		intron_variant			NP_001310529.1
SVIL	NM_003174.3	c.-50-3410G>C		intron_variant			NP_003165.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SVIL	ENST00000355867.9	c.-50-3410G>C		intron_variant		1	NM_021738.3	ENSP00000348128.4

Frequencies

GnomAD3 genomes AF: 0.300 AC: 45467 AN: 151722 Hom.: 7084 Cov.: 32

Gnomad AFR AF: 0.385

Gnomad AMI AF: 0.500

Gnomad AMR AF: 0.287

Gnomad ASJ AF: 0.151

Gnomad EAS AF: 0.329

Gnomad SAS AF: 0.250

Gnomad FIN AF: 0.293

Gnomad MID AF: 0.220

Gnomad NFE AF: 0.259

Gnomad OTH AF: 0.272

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

GnomAD4 genome AF: 0.300 AC: 45497 AN: 151842 Hom.: 7092 Cov.: 32 AF XY: 0.300 AC XY: 22236 AN XY: 74218

Gnomad4 AFR AF: 0.385

Gnomad4 AMR AF: 0.287

Gnomad4 ASJ AF: 0.151

Gnomad4 EAS AF: 0.330

Gnomad4 SAS AF: 0.247

Gnomad4 FIN AF: 0.293

Gnomad4 NFE AF: 0.259

Gnomad4 OTH AF: 0.269

Alfa AF: 0.283 Hom.: 812

Bravo AF: 0.304

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.0
DANN	Benign	0.67

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: rs7903397; hg19: chr10-29847447;