rs6877118

Positions:

• chr5-156612978-G-A
• chr5-156612978-G-C
• chr5-156612978-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000337851.9(SGCD):​c.502+17927G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0572 in 152,190 control chromosomes in the GnomAD database, including 574 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 0.057 (574 hom., cov: 33)
• Consequence: SGCD ENST00000337851.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.515

Genes affected

SGCD (HGNC:10807): (sarcoglycan delta) The protein encoded by this gene is one of the four known components of the sarcoglycan complex, which is a subcomplex of the dystrophin-glycoprotein complex (DGC). DGC forms a link between the F-actin cytoskeleton and the extracellular matrix. This protein is expressed most abundantly in skeletal and cardiac muscle. Mutations in this gene have been associated with autosomal recessive limb-girdle muscular dystrophy and dilated cardiomyopathy. Alternatively spliced transcript variants encoding distinct isoforms have been observed for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.207 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SGCD	NM_000337.6	c.502+17927G>A		intron_variant		ENST00000337851.9	NP_000328.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SGCD	ENST00000337851.9	c.502+17927G>A		intron_variant		1	NM_000337.6	ENSP00000338343	P4
SGCD	ENST00000435422.7	c.499+17927G>A		intron_variant		1		ENSP00000403003	A1
SGCD	ENST00000517913.5	c.502+17927G>A		intron_variant		5		ENSP00000429378

Frequencies

GnomAD3 genomes AF: 0.0571 AC: 8678 AN: 152072 Hom.: 572 Cov.: 33

Gnomad AFR AF: 0.138

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0393

Gnomad ASJ AF: 0.0115

Gnomad EAS AF: 0.216

Gnomad SAS AF: 0.0361

Gnomad FIN AF: 0.00622

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0127

Gnomad OTH AF: 0.0545

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

GnomAD4 genome AF: 0.0572 AC: 8705 AN: 152190 Hom.: 574 Cov.: 33 AF XY: 0.0575 AC XY: 4280 AN XY: 74404

Gnomad4 AFR AF: 0.138

Gnomad4 AMR AF: 0.0393

Gnomad4 ASJ AF: 0.0115

Gnomad4 EAS AF: 0.217

Gnomad4 SAS AF: 0.0360

Gnomad4 FIN AF: 0.00622

Gnomad4 NFE AF: 0.0127

Gnomad4 OTH AF: 0.0539

Alfa AF: 0.0104 Hom.: 10

Bravo AF: 0.0647

Asia WGS AF: 0.100 AC: 348 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	4.3
DANN	Benign	0.37

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

Publications

LitVar

Other links and lift over

dbSNP: rs6877118; hg19: chr5-156039988; COSMIC: COSV61913219;