rs4704970

Variant names:

• chr5-156073982-G-A
• rs4704970
• ENST00000517913.5:c.-281-43896G>A

Variant summary

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

The ENST00000517913.5(SGCD):​c.-281-43896G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.141 in 152,218 control chromosomes in the GnomAD database, including 1,802 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. The gene SGCD is included in the ClinGen Criteria Specification Registry.

• Frequency: Genomes: 𝑓 0.14 (1802 hom., cov: 32)
• Consequence: SGCD ENST00000517913.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.107
• Publications: 16 publications found

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]

SGCD Gene-Disease associations (from GenCC):

• autosomal recessive limb-girdle muscular dystrophy

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: PanelApp Australia, ClinGen
• autosomal recessive limb-girdle muscular dystrophy type 2F

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Myriad Women's Health, Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae)
• familial isolated dilated cardiomyopathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• dilated cardiomyopathy

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen
• dilated cardiomyopathy 1L

  Inheritance: AD Classification: NO_KNOWN Submitted by: Ambry Genetics

ACMG classification

Specifications for SGCD are available in the ClinGen Criteria Specification Registry and recommended for reference when assigning criteria.

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.184 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000517913.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SGCD	ENST00000517913.5	TSL:5	c.-281-43896G>A		intron	N/A	ENSP00000429378.1	Q92629-3

Frequencies

GnomAD3 genomes AF: 0.142 AC: 21523 AN: 152100 Hom.: 1802 Cov.: 32

Gnomad AFR AF: 0.0745

Gnomad AMI AF: 0.115

Gnomad AMR AF: 0.122

Gnomad ASJ AF: 0.187

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0948

Gnomad FIN AF: 0.214

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.187

Gnomad OTH AF: 0.144

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

GnomAD4 genome AF: 0.141 AC: 21523 AN: 152218 Hom.: 1802 Cov.: 32 AF XY: 0.140 AC XY: 10397 AN XY: 74424

African (AFR) AF: 0.0746 AC: 3098 AN: 41552

American (AMR) AF: 0.122 AC: 1867 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.187 AC: 649 AN: 3468

East Asian (EAS) AF: 0.00135 AC: 7 AN: 5188

South Asian (SAS) AF: 0.0949 AC: 458 AN: 4826

European-Finnish (FIN) AF: 0.214 AC: 2266 AN: 10586

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.187 AC: 12722 AN: 67988

Other (OTH) AF: 0.141 AC: 298 AN: 2116

Alfa AF: 0.167 Hom.: 5299

Bravo AF: 0.131

Asia WGS AF: 0.0560 AC: 197 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	6.6
DANN	Benign	0.73
PhyloP100		0.11
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs4704970;

hg19: chr5-155500992;

COSMIC: COSV72991171;