rs1247441

Variant names:

• chr10-29610854-T-C
• rs1247441
• NM_021738.3:c.-201+23566A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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 Gene-Disease associations (from GenCC):

• myofibrillar myopathy 10

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
SVIL	NM_021738.3	c.-201+23566A>G		intron_variant	Intron 1 of 37	ENST00000355867.9	NP_068506.2
SVIL	NM_001323599.2	c.-200-41542A>G		intron_variant	Intron 3 of 38		NP_001310528.1
SVIL	NM_001323600.1	c.-200-41542A>G		intron_variant	Intron 3 of 36		NP_001310529.1
SVIL	NM_003174.3	c.-200-41542A>G		intron_variant	Intron 3 of 35		NP_003165.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SVIL	ENST00000355867.9	c.-201+23566A>G		intron_variant	Intron 1 of 37	1	NM_021738.3	ENSP00000348128.4

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

African (AFR) AF: 0.469 AC: 19425 AN: 41416

American (AMR) AF: 0.429 AC: 6548 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.397 AC: 1375 AN: 3462

East Asian (EAS) AF: 0.344 AC: 1770 AN: 5138

South Asian (SAS) AF: 0.227 AC: 1095 AN: 4822

European-Finnish (FIN) AF: 0.440 AC: 4643 AN: 10554

Middle Eastern (MID) AF: 0.265 AC: 78 AN: 294

European-Non Finnish (NFE) AF: 0.410 AC: 27849 AN: 67954

Other (OTH) AF: 0.409 AC: 862 AN: 2110

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
PhyloP100		-0.72
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1247441; hg19: chr10-29899783;