rs9664986

chr10-29581095-A-G

Variant summary

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

The NM_021738.3(SVIL):c.-200-11783T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.147 in 152,258 control chromosomes in the GnomAD database, including 1,720 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 0.15 (1720 hom., cov: 33)
• Consequence: SVIL NM_021738.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.270

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=-0.84).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.219 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SVIL	NM_021738.3	c.-200-11783T>C		intron_variant		ENST00000355867.9
SVIL	NM_001323599.2	c.-200-11783T>C		intron_variant
SVIL	NM_001323600.1	c.-200-11783T>C		intron_variant
SVIL	NM_003174.3	c.-200-11783T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SVIL	ENST00000355867.9	c.-200-11783T>C		intron_variant		1	NM_021738.3	A2

Frequencies

GnomAD3 genomes AF: 0.147 AC: 22383 AN: 152140 Hom.: 1710 Cov.: 33

Gnomad AFR AF: 0.130

Gnomad AMI AF: 0.0428

Gnomad AMR AF: 0.225

Gnomad ASJ AF: 0.111

Gnomad EAS AF: 0.171

Gnomad SAS AF: 0.147

Gnomad FIN AF: 0.137

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.144

Gnomad OTH AF: 0.150

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

GnomAD4 genome AF: 0.147 AC: 22437 AN: 152258 Hom.: 1720 Cov.: 33 AF XY: 0.148 AC XY: 11025 AN XY: 74440

Gnomad4 AFR AF: 0.130

Gnomad4 AMR AF: 0.226

Gnomad4 ASJ AF: 0.111

Gnomad4 EAS AF: 0.171

Gnomad4 SAS AF: 0.147

Gnomad4 FIN AF: 0.137

Gnomad4 NFE AF: 0.143

Gnomad4 OTH AF: 0.155

Alfa AF: 0.148 Hom.: 728

Bravo AF: 0.153

Asia WGS AF: 0.161 AC: 557 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	4.6
Dann	Benign	0.72

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: rs9664986; hg19: chr10-29870024;