rs4704951

Positions:

• chr5-156057657-A-G

Variant summary

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

The ENST00000517913.5(SGCD):​c.-281-60221A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0343 in 146,440 control chromosomes in the GnomAD database, including 880 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 0.034 (880 hom., cov: 29)
• Consequence: SGCD ENST00000517913.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.148

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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.451 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SGCD	XM_017009724.2	c.-207-66199A>G		intron_variant
SGCD	XM_047417518.1	c.-208+22502A>G		intron_variant
SGCD	XM_047417519.1	c.-207-66199A>G		intron_variant
SGCD	XM_047417520.1	c.-164-66199A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SGCD	ENST00000517913.5	c.-281-60221A>G		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.0344 AC: 5027 AN: 146324 Hom.: 881 Cov.: 29

Gnomad AFR AF: 0.00386

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0422

Gnomad ASJ AF: 0.0117

Gnomad EAS AF: 0.468

Gnomad SAS AF: 0.140

Gnomad FIN AF: 0.0634

Gnomad MID AF: 0.00671

Gnomad NFE AF: 0.00722

Gnomad OTH AF: 0.0311

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

GnomAD4 genome AF: 0.0343 AC: 5022 AN: 146440 Hom.: 880 Cov.: 29 AF XY: 0.0415 AC XY: 2961 AN XY: 71354

Gnomad4 AFR AF: 0.00387

Gnomad4 AMR AF: 0.0421

Gnomad4 ASJ AF: 0.0117

Gnomad4 EAS AF: 0.467

Gnomad4 SAS AF: 0.138

Gnomad4 FIN AF: 0.0634

Gnomad4 NFE AF: 0.00726

Gnomad4 OTH AF: 0.0347

Alfa AF: 0.0180 Hom.: 39

Asia WGS AF: 0.250 AC: 860 AN: 3444

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.8
DANN	Benign	0.79

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4704951; hg19: chr5-155484667;