rs6875111

Variant names:

• chr5-155826870-G-A
• rs6875111
• ENST00000755060.1:n.508+4781G>A

Variant summary

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

The ENST00000755060.1(ENSG00000298352):​n.508+4781G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.117 in 152,156 control chromosomes in the GnomAD database, including 2,146 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 0.12 (2146 hom., cov: 33)
• Consequence: ENSG00000298352 ENST00000755060.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.416
• 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.301 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000755060.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000298352	ENST00000755060.1		n.508+4781G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.117 AC: 17715 AN: 152038 Hom.: 2141 Cov.: 33

Gnomad AFR AF: 0.305

Gnomad AMI AF: 0.0793

Gnomad AMR AF: 0.0646

Gnomad ASJ AF: 0.0473

Gnomad EAS AF: 0.178

Gnomad SAS AF: 0.0899

Gnomad FIN AF: 0.0249

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0298

Gnomad OTH AF: 0.0979

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

GnomAD4 genome AF: 0.117 AC: 17742 AN: 152156 Hom.: 2146 Cov.: 33 AF XY: 0.115 AC XY: 8545 AN XY: 74388

African (AFR) AF: 0.305 AC: 12651 AN: 41478

American (AMR) AF: 0.0645 AC: 986 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0473 AC: 164 AN: 3468

East Asian (EAS) AF: 0.178 AC: 921 AN: 5176

South Asian (SAS) AF: 0.0898 AC: 433 AN: 4822

European-Finnish (FIN) AF: 0.0249 AC: 264 AN: 10596

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.0297 AC: 2023 AN: 68012

Other (OTH) AF: 0.0988 AC: 209 AN: 2116

Alfa AF: 0.0600 Hom.: 2930

Bravo AF: 0.131

Asia WGS AF: 0.161 AC: 557 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.3
DANN	Benign	0.60
PhyloP100		0.42

Splicing

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

Other links and lift over

dbSNP: rs6875111; hg19: chr5-155253880;