ENST00000517913.5:c.-281-74442T>C

Variant names:

• chr5-156043436-T-C
• rs4704943
• ENST00000517913.5:c.-281-74442T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 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 Submitted by: ClinGen
• autosomal recessive limb-girdle muscular dystrophy type 2F

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

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

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

  Inheritance: AD Classification: NO_KNOWN Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
SGCD	XM_017009724.2	c.-207-80420T>C		intron_variant	Intron 1 of 9		XP_016865213.1
SGCD	XM_047417518.1	c.-208+8281T>C		intron_variant	Intron 3 of 11		XP_047273474.1
SGCD	XM_047417519.1	c.-207-80420T>C		intron_variant	Intron 2 of 10		XP_047273475.1
SGCD	XM_047417520.1	c.-164-80420T>C		intron_variant	Intron 1 of 8		XP_047273476.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SGCD	ENST00000517913.5	c.-281-74442T>C		intron_variant	Intron 1 of 9	5		ENSP00000429378.1

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

African (AFR) AF: 0.549 AC: 22723 AN: 41408

American (AMR) AF: 0.201 AC: 3073 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.233 AC: 807 AN: 3468

East Asian (EAS) AF: 0.00347 AC: 18 AN: 5182

South Asian (SAS) AF: 0.124 AC: 599 AN: 4824

European-Finnish (FIN) AF: 0.234 AC: 2477 AN: 10582

Middle Eastern (MID) AF: 0.259 AC: 76 AN: 294

European-Non Finnish (NFE) AF: 0.227 AC: 15432 AN: 67972

Other (OTH) AF: 0.278 AC: 587 AN: 2108

Alfa AF: 0.253 Hom.: 3138

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
PhyloP100		0.064
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

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