5-155775518-A-G

Variant names:

• chr5-155775518-A-G
• rs11134474
• ENST00000755060.1:n.471+46528A>G

Variant summary

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

The ENST00000755060.1(ENSG00000298352):​n.471+46528A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0446 in 152,112 control chromosomes in the GnomAD database, including 325 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 0.045 (325 hom., cov: 32)
• Consequence: ENSG00000298352 ENST00000755060.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0780
• Publications: 2 publications found

Genes affected

ENSG00000298352 (HGNC:):

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=-0.65).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.115 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SGCD	XM_017009724.2	c.-208+46528A>G		intron_variant	Intron 1 of 9		XP_016865213.1
SGCD	XM_047417518.1	c.-345+46528A>G		intron_variant	Intron 1 of 11		XP_047273474.1
SGCD	XM_047417519.1	c.-289+46528A>G		intron_variant	Intron 1 of 10		XP_047273475.1
SGCD	XM_047417520.1	c.-165+46528A>G		intron_variant	Intron 1 of 8		XP_047273476.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000298352	ENST00000755060.1	n.471+46528A>G		intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes AF: 0.0445 AC: 6765 AN: 151994 Hom.: 324 Cov.: 32

Gnomad AFR AF: 0.118

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0273

Gnomad ASJ AF: 0.0418

Gnomad EAS AF: 0.0465

Gnomad SAS AF: 0.0436

Gnomad FIN AF: 0.00349

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0109

Gnomad OTH AF: 0.0464

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

GnomAD4 genome AF: 0.0446 AC: 6785 AN: 152112 Hom.: 325 Cov.: 32 AF XY: 0.0436 AC XY: 3244 AN XY: 74346

African (AFR) AF: 0.118 AC: 4887 AN: 41480

American (AMR) AF: 0.0273 AC: 417 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.0418 AC: 145 AN: 3470

East Asian (EAS) AF: 0.0466 AC: 241 AN: 5172

South Asian (SAS) AF: 0.0436 AC: 210 AN: 4816

European-Finnish (FIN) AF: 0.00349 AC: 37 AN: 10592

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.0109 AC: 739 AN: 67986

Other (OTH) AF: 0.0468 AC: 99 AN: 2114

Alfa AF: 0.0219 Hom.: 292

Bravo AF: 0.0510

Asia WGS AF: 0.0530 AC: 184 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	8.4
DANN	Benign	0.78
PhyloP100		0.078

Splicing

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

Other links and lift over

dbSNP: rs11134474; hg19: chr5-155202528;