10-29678717-T-C

Variant names:

• chr10-29678717-T-C
• rs7358069
• ENST00000375400.7:c.-301+7836A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000375400.7(SVIL):​c.-301+7836A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.27 in 152,176 control chromosomes in the GnomAD database, including 5,605 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 0.27 (5605 hom., cov: 32)
• Consequence: SVIL ENST00000375400.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.424
• Publications: 1 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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.359 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SVIL	NM_001323599.2	c.-301+7836A>G		intron_variant	Intron 2 of 38		NP_001310528.1
SVIL	NM_001323600.1	c.-301+7836A>G		intron_variant	Intron 2 of 36		NP_001310529.1
SVIL	NM_003174.3	c.-301+7836A>G		intron_variant	Intron 2 of 35		NP_003165.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SVIL	ENST00000375400.7	c.-301+7836A>G		intron_variant	Intron 2 of 35	1		ENSP00000364549.3
SVIL	ENST00000674475.1	c.-301+7836A>G		intron_variant	Intron 2 of 38			ENSP00000501521.1
SVIL	ENST00000674490.1	c.-301+7836A>G		intron_variant	Intron 2 of 5			ENSP00000501398.1

Frequencies

GnomAD3 genomes AF: 0.270 AC: 41034 AN: 152058 Hom.: 5601 Cov.: 32

Gnomad AFR AF: 0.266

Gnomad AMI AF: 0.135

Gnomad AMR AF: 0.246

Gnomad ASJ AF: 0.209

Gnomad EAS AF: 0.373

Gnomad SAS AF: 0.221

Gnomad FIN AF: 0.285

Gnomad MID AF: 0.290

Gnomad NFE AF: 0.276

Gnomad OTH AF: 0.256

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

GnomAD4 genome AF: 0.270 AC: 41064 AN: 152176 Hom.: 5605 Cov.: 32 AF XY: 0.274 AC XY: 20344 AN XY: 74374

African (AFR) AF: 0.266 AC: 11058 AN: 41520

American (AMR) AF: 0.245 AC: 3756 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.209 AC: 727 AN: 3472

East Asian (EAS) AF: 0.373 AC: 1931 AN: 5172

South Asian (SAS) AF: 0.222 AC: 1070 AN: 4824

European-Finnish (FIN) AF: 0.285 AC: 3024 AN: 10592

Middle Eastern (MID) AF: 0.291 AC: 85 AN: 292

European-Non Finnish (NFE) AF: 0.276 AC: 18747 AN: 67984

Other (OTH) AF: 0.257 AC: 543 AN: 2112

Alfa AF: 0.274 Hom.: 4448

Bravo AF: 0.271

Asia WGS AF: 0.301 AC: 1047 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	7.8
DANN	Benign	0.82
PhyloP100		0.42
Mutation Taster		=99/1	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs7358069; hg19: chr10-29967646;