rs1121853

Variant names:

• chr5-156258902-A-G
• rs1121853
• ENST00000959782.1:c.-44+6682A>G

Variant summary

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

The ENST00000959782.1(SGCD):​c.-44+6682A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0654 in 152,060 control chromosomes in the GnomAD database, including 326 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 0.065 (326 hom., cov: 32)
• Consequence: SGCD ENST00000959782.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.240
• Publications: 1 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=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0705 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000959782.1. 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	ENST00000959782.1		c.-44+6682A>G		intron	N/A	ENSP00000629841.1
	SGCD	ENST00000517913.5	TSL:5	c.-43-70632A>G		intron	N/A	ENSP00000429378.1	Q92629-3

Frequencies

GnomAD3 genomes AF: 0.0655 AC: 9949 AN: 151946 Hom.: 325 Cov.: 32

Gnomad AFR AF: 0.0727

Gnomad AMI AF: 0.0757

Gnomad AMR AF: 0.0450

Gnomad ASJ AF: 0.0323

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0329

Gnomad FIN AF: 0.104

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0688

Gnomad OTH AF: 0.0588

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

GnomAD4 genome AF: 0.0654 AC: 9952 AN: 152060 Hom.: 326 Cov.: 32 AF XY: 0.0645 AC XY: 4793 AN XY: 74348

African (AFR) AF: 0.0727 AC: 3019 AN: 41532

American (AMR) AF: 0.0450 AC: 686 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.0323 AC: 112 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5170

South Asian (SAS) AF: 0.0326 AC: 157 AN: 4822

European-Finnish (FIN) AF: 0.104 AC: 1099 AN: 10544

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.0688 AC: 4675 AN: 67944

Other (OTH) AF: 0.0582 AC: 123 AN: 2114

Alfa AF: 0.0686 Hom.: 43

Bravo AF: 0.0625

Asia WGS AF: 0.0210 AC: 72 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	8.0
DANN	Benign	0.86
PhyloP100		0.24
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: rs1121853;

hg19: chr5-155685912;