10-29719734-T-C

Variant names:

• chr10-29719734-T-C
• rs1927457
• ENST00000375400.7:c.-400+16017A>G

Variant summary

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

The ENST00000375400.7(SVIL):​c.-400+16017A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.332 in 151,870 control chromosomes in the GnomAD database, including 8,732 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 0.33 (8732 hom., cov: 32)
• Consequence: SVIL ENST00000375400.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.16
• Publications: 12 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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.462 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SVIL	NM_001323599.2	c.-400+16951A>G		intron_variant	Intron 1 of 38		NP_001310528.1
SVIL	NM_001323600.1	c.-400+16021A>G		intron_variant	Intron 1 of 36		NP_001310529.1
SVIL	NM_003174.3	c.-400+16017A>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.-400+16017A>G		intron_variant	Intron 1 of 35	1		ENSP00000364549.3
SVIL	ENST00000674475.1	c.-400+16951A>G		intron_variant	Intron 1 of 38			ENSP00000501521.1
SVIL	ENST00000674490.1	c.-400+16021A>G		intron_variant	Intron 1 of 5			ENSP00000501398.1

Frequencies

GnomAD3 genomes AF: 0.332 AC: 50404 AN: 151752 Hom.: 8727 Cov.: 32

Gnomad AFR AF: 0.398

Gnomad AMI AF: 0.301

Gnomad AMR AF: 0.284

Gnomad ASJ AF: 0.286

Gnomad EAS AF: 0.480

Gnomad SAS AF: 0.416

Gnomad FIN AF: 0.266

Gnomad MID AF: 0.361

Gnomad NFE AF: 0.299

Gnomad OTH AF: 0.326

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

GnomAD4 genome AF: 0.332 AC: 50434 AN: 151870 Hom.: 8732 Cov.: 32 AF XY: 0.333 AC XY: 24718 AN XY: 74222

African (AFR) AF: 0.398 AC: 16454 AN: 41374

American (AMR) AF: 0.283 AC: 4320 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.286 AC: 989 AN: 3464

East Asian (EAS) AF: 0.478 AC: 2470 AN: 5166

South Asian (SAS) AF: 0.416 AC: 2005 AN: 4818

European-Finnish (FIN) AF: 0.266 AC: 2795 AN: 10522

Middle Eastern (MID) AF: 0.374 AC: 110 AN: 294

European-Non Finnish (NFE) AF: 0.299 AC: 20339 AN: 67972

Other (OTH) AF: 0.322 AC: 679 AN: 2108

Alfa AF: 0.312 Hom.: 30188

Bravo AF: 0.335

Asia WGS AF: 0.416 AC: 1449 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.092
DANN	Benign	0.90
PhyloP100		-2.2
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: rs1927457; hg19: chr10-30008663;