rs1415130

Variant names:

• chr13-23179740-C-T
• rs1415130
• NM_001378244.1:c.54+19094C>T

Variant summary

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

The NM_001378244.1(SGCG):​c.54+19094C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.213 in 151,958 control chromosomes in the GnomAD database, including 4,091 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 0.21 (4091 hom., cov: 32)
• Consequence: SGCG NM_001378244.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.19
• Publications: 4 publications found

Genes affected

SGCG (HGNC:10809): (sarcoglycan gamma) This gene encodes gamma-sarcoglycan, one of several sarcolemmal transmembrane glycoproteins that interact with dystrophin. The dystrophin-glycoprotein complex (DGC) spans the sarcolemma and is comprised of dystrophin, syntrophin, alpha- and beta-dystroglycans and sarcoglycans. The DGC provides a structural link between the subsarcolemmal cytoskeleton and the extracellular matrix of muscle cells. Defects in the encoded protein can lead to early onset autosomal recessive muscular dystrophy, in particular limb-girdle muscular dystrophy, type 2C (LGMD2C). [provided by RefSeq, Oct 2008]

SGCG Gene-Disease associations (from GenCC):

• autosomal recessive limb-girdle muscular dystrophy

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• autosomal recessive limb-girdle muscular dystrophy type 2C

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Myriad Women’s Health, Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.309 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SGCG	NM_001378244.1	c.54+19094C>T		intron_variant	Intron 1 of 7		NP_001365173.1
SGCG	XM_047430542.1	c.54+19094C>T		intron_variant	Intron 1 of 6		XP_047286498.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.213 AC: 32298 AN: 151840 Hom.: 4091 Cov.: 32

Gnomad AFR AF: 0.0787

Gnomad AMI AF: 0.196

Gnomad AMR AF: 0.217

Gnomad ASJ AF: 0.228

Gnomad EAS AF: 0.323

Gnomad SAS AF: 0.279

Gnomad FIN AF: 0.272

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.270

Gnomad OTH AF: 0.220

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

GnomAD4 genome AF: 0.213 AC: 32304 AN: 151958 Hom.: 4091 Cov.: 32 AF XY: 0.214 AC XY: 15885 AN XY: 74238

African (AFR) AF: 0.0787 AC: 3264 AN: 41488

American (AMR) AF: 0.217 AC: 3312 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.228 AC: 789 AN: 3468

East Asian (EAS) AF: 0.322 AC: 1658 AN: 5150

South Asian (SAS) AF: 0.281 AC: 1351 AN: 4816

European-Finnish (FIN) AF: 0.272 AC: 2854 AN: 10488

Middle Eastern (MID) AF: 0.245 AC: 72 AN: 294

European-Non Finnish (NFE) AF: 0.270 AC: 18364 AN: 67964

Other (OTH) AF: 0.218 AC: 461 AN: 2114

Alfa AF: 0.233 Hom.: 1715

Bravo AF: 0.202

Asia WGS AF: 0.291 AC: 1011 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	18
DANN	Benign	0.60
PhyloP100		2.2

Splicing

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

Other links and lift over

dbSNP: rs1415130; hg19: chr13-23753879; COSMIC: COSV54562984;