rs249888

Variant names:

• chr5-156239784-C-T
• rs249888
• ENST00000517913.5:c.-43-89750C>T

Variant summary

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

The ENST00000517913.5(SGCD):​c.-43-89750C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.261 in 152,028 control chromosomes in the GnomAD database, including 5,642 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 0.26 (5642 hom., cov: 32)
• Consequence: SGCD ENST00000517913.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.828
• 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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.306 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SGCD	XM_017009724.2	c.-43-89750C>T		intron_variant	Intron 2 of 9		XP_016865213.1
SGCD	XM_047417518.1	c.-43-89750C>T		intron_variant	Intron 4 of 11		XP_047273474.1
SGCD	XM_047417519.1	c.-43-89750C>T		intron_variant	Intron 3 of 10		XP_047273475.1
SGCD	XM_047417520.1	c.1-104705C>T		intron_variant	Intron 2 of 8		XP_047273476.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SGCD	ENST00000517913.5	c.-43-89750C>T		intron_variant	Intron 3 of 9	5		ENSP00000429378.1

Frequencies

GnomAD3 genomes AF: 0.261 AC: 39614 AN: 151910 Hom.: 5643 Cov.: 32

Gnomad AFR AF: 0.189

Gnomad AMI AF: 0.269

Gnomad AMR AF: 0.298

Gnomad ASJ AF: 0.260

Gnomad EAS AF: 0.0696

Gnomad SAS AF: 0.177

Gnomad FIN AF: 0.305

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.310

Gnomad OTH AF: 0.254

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

GnomAD4 genome AF: 0.261 AC: 39632 AN: 152028 Hom.: 5642 Cov.: 32 AF XY: 0.258 AC XY: 19149 AN XY: 74284

African (AFR) AF: 0.189 AC: 7831 AN: 41460

American (AMR) AF: 0.299 AC: 4561 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.260 AC: 903 AN: 3472

East Asian (EAS) AF: 0.0697 AC: 361 AN: 5178

South Asian (SAS) AF: 0.179 AC: 861 AN: 4820

European-Finnish (FIN) AF: 0.305 AC: 3215 AN: 10536

Middle Eastern (MID) AF: 0.207 AC: 61 AN: 294

European-Non Finnish (NFE) AF: 0.310 AC: 21067 AN: 67970

Other (OTH) AF: 0.250 AC: 527 AN: 2110

Alfa AF: 0.293 Hom.: 11235

Bravo AF: 0.257

Asia WGS AF: 0.141 AC: 493 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.72
DANN	Benign	0.28
PhyloP100		-0.83
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: rs249888; hg19: chr5-155666794;