rs4704943

Positions:

• chr5-156043436-T-C

Variant summary

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

The ENST00000517913.5(SGCD):​c.-281-74442T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.302 in 152,018 control chromosomes in the GnomAD database, including 8,896 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 0.30 (8896 hom., cov: 32)
• Consequence: SGCD ENST00000517913.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0640

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=-0.71).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.543 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SGCD	XM_017009724.2	c.-207-80420T>C		intron_variant			XP_016865213.1
SGCD	XM_047417518.1	c.-208+8281T>C		intron_variant			XP_047273474.1
SGCD	XM_047417519.1	c.-207-80420T>C		intron_variant			XP_047273475.1
SGCD	XM_047417520.1	c.-164-80420T>C		intron_variant			XP_047273476.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SGCD	ENST00000517913.5	c.-281-74442T>C		intron_variant		5		ENSP00000429378

Frequencies

GnomAD3 genomes AF: 0.302 AC: 45831 AN: 151900 Hom.: 8862 Cov.: 32

Gnomad AFR AF: 0.548

Gnomad AMI AF: 0.124

Gnomad AMR AF: 0.202

Gnomad ASJ AF: 0.233

Gnomad EAS AF: 0.00347

Gnomad SAS AF: 0.124

Gnomad FIN AF: 0.234

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.227

Gnomad OTH AF: 0.283

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

GnomAD4 genome AF: 0.302 AC: 45905 AN: 152018 Hom.: 8896 Cov.: 32 AF XY: 0.296 AC XY: 21985 AN XY: 74332

Gnomad4 AFR AF: 0.549

Gnomad4 AMR AF: 0.201

Gnomad4 ASJ AF: 0.233

Gnomad4 EAS AF: 0.00347

Gnomad4 SAS AF: 0.124

Gnomad4 FIN AF: 0.234

Gnomad4 NFE AF: 0.227

Gnomad4 OTH AF: 0.278

Alfa AF: 0.251 Hom.: 2757

Bravo AF: 0.310

Asia WGS AF: 0.0980 AC: 343 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	9.5
DANN	Benign	0.67

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4704943; hg19: chr5-155470446; COSMIC: COSV72991155;