rs1247441

Positions:

• chr10-29610854-T-C

Variant summary

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

The NM_021738.3(SVIL):​c.-201+23566A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.422 in 151,920 control chromosomes in the GnomAD database, including 13,700 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 0.42 (13700 hom., cov: 31)
• Consequence: SVIL NM_021738.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.717

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=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.463 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SVIL	NM_021738.3	c.-201+23566A>G		intron_variant		ENST00000355867.9	NP_068506.2
SVIL	NM_001323599.2	c.-200-41542A>G		intron_variant			NP_001310528.1
SVIL	NM_001323600.1	c.-200-41542A>G		intron_variant			NP_001310529.1
SVIL	NM_003174.3	c.-200-41542A>G		intron_variant			NP_003165.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SVIL	ENST00000355867.9	c.-201+23566A>G		intron_variant		1	NM_021738.3	ENSP00000348128	A2

Frequencies

GnomAD3 genomes AF: 0.422 AC: 63985 AN: 151802 Hom.: 13677 Cov.: 31

Gnomad AFR AF: 0.469

Gnomad AMI AF: 0.461

Gnomad AMR AF: 0.429

Gnomad ASJ AF: 0.397

Gnomad EAS AF: 0.345

Gnomad SAS AF: 0.227

Gnomad FIN AF: 0.440

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.410

Gnomad OTH AF: 0.409

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

GnomAD4 genome AF: 0.422 AC: 64065 AN: 151920 Hom.: 13700 Cov.: 31 AF XY: 0.417 AC XY: 30973 AN XY: 74244

Gnomad4 AFR AF: 0.469

Gnomad4 AMR AF: 0.429

Gnomad4 ASJ AF: 0.397

Gnomad4 EAS AF: 0.344

Gnomad4 SAS AF: 0.227

Gnomad4 FIN AF: 0.440

Gnomad4 NFE AF: 0.410

Gnomad4 OTH AF: 0.409

Alfa AF: 0.417 Hom.: 2245

Bravo AF: 0.426

Asia WGS AF: 0.275 AC: 959 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	1.3
DANN	Benign	0.47

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: rs1247441; hg19: chr10-29899783;