ENST00000375400.7:c.-399-7374T>G

Variant names:

• chr10-29694025-A-C
• rs6481619
• ENST00000375400.7:c.-399-7374T>G

Variant summary

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

The ENST00000375400.7(SVIL):​c.-399-7374T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.25 in 151,808 control chromosomes in the GnomAD database, including 4,849 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 0.25 (4849 hom., cov: 30)
• Consequence: SVIL ENST00000375400.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.427
• Publications: 4 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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.357 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SVIL	NM_001323599.2	c.-399-7374T>G		intron_variant	Intron 1 of 38		NP_001310528.1
SVIL	NM_001323600.1	c.-399-7374T>G		intron_variant	Intron 1 of 36		NP_001310529.1
SVIL	NM_003174.3	c.-399-7374T>G		intron_variant	Intron 1 of 35		NP_003165.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SVIL	ENST00000375400.7	c.-399-7374T>G		intron_variant	Intron 1 of 35	1		ENSP00000364549.3
SVIL	ENST00000674475.1	c.-399-7374T>G		intron_variant	Intron 1 of 38			ENSP00000501521.1
SVIL	ENST00000674490.1	c.-399-7374T>G		intron_variant	Intron 1 of 5			ENSP00000501398.1

Frequencies

GnomAD3 genomes AF: 0.250 AC: 37851 AN: 151690 Hom.: 4846 Cov.: 30

Gnomad AFR AF: 0.201

Gnomad AMI AF: 0.136

Gnomad AMR AF: 0.239

Gnomad ASJ AF: 0.209

Gnomad EAS AF: 0.370

Gnomad SAS AF: 0.221

Gnomad FIN AF: 0.284

Gnomad MID AF: 0.287

Gnomad NFE AF: 0.273

Gnomad OTH AF: 0.240

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

GnomAD4 genome AF: 0.250 AC: 37880 AN: 151808 Hom.: 4849 Cov.: 30 AF XY: 0.254 AC XY: 18825 AN XY: 74162

African (AFR) AF: 0.201 AC: 8303 AN: 41388

American (AMR) AF: 0.238 AC: 3640 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.209 AC: 725 AN: 3472

East Asian (EAS) AF: 0.371 AC: 1897 AN: 5120

South Asian (SAS) AF: 0.222 AC: 1066 AN: 4806

European-Finnish (FIN) AF: 0.284 AC: 2987 AN: 10514

Middle Eastern (MID) AF: 0.286 AC: 84 AN: 294

European-Non Finnish (NFE) AF: 0.273 AC: 18545 AN: 67932

Other (OTH) AF: 0.242 AC: 509 AN: 2106

Alfa AF: 0.261 Hom.: 14894

Bravo AF: 0.248

Asia WGS AF: 0.293 AC: 1021 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.6
DANN	Benign	0.69
PhyloP100		0.43
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs6481619; hg19: chr10-29982954;