ENST00000517913.5:c.-281-60221A>G

Variant names:

• chr5-156057657-A-G
• rs4704951
• ENST00000517913.5:c.-281-60221A>G

Variant summary

Our verdict is Benign. The variant received -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
• 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 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=-0.86).
• 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 rank	MANE	Protein	UniProt
SGCD	XM_017009724.2	c.-207-66199A>G		intron_variant	Intron 1 of 9		XP_016865213.1
SGCD	XM_047417518.1	c.-208+22502A>G		intron_variant	Intron 3 of 11		XP_047273474.1
SGCD	XM_047417519.1	c.-207-66199A>G		intron_variant	Intron 2 of 10		XP_047273475.1
SGCD	XM_047417520.1	c.-164-66199A>G		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.-281-60221A>G		intron_variant	Intron 1 of 9	5		ENSP00000429378.1

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

African (AFR) AF: 0.00387 AC: 158 AN: 40788

American (AMR) AF: 0.0421 AC: 619 AN: 14690

Ashkenazi Jewish (ASJ) AF: 0.0117 AC: 39 AN: 3336

East Asian (EAS) AF: 0.467 AC: 2403 AN: 5146

South Asian (SAS) AF: 0.138 AC: 644 AN: 4656

European-Finnish (FIN) AF: 0.0634 AC: 616 AN: 9718

Middle Eastern (MID) AF: 0.00714 AC: 2 AN: 280

European-Non Finnish (NFE) AF: 0.00726 AC: 471 AN: 64912

Other (OTH) AF: 0.0347 AC: 70 AN: 2016

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
PhyloP100		0.15
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: rs4704951; hg19: chr5-155484667;