rs149976574

Variant names:

• chr5-156326646-CTGTAATAAGCT-C
• rs149976574
• ENST00000959782.1:c.-43-2887_-43-2877delTGTAATAAGCT

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The ENST00000959782.1(SGCD):​c.-43-2887_-43-2877delTGTAATAAGCT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0182 in 152,242 control chromosomes in the GnomAD database, including 313 homozygotes. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Likely benign (★★). The gene SGCD is included in the ClinGen Criteria Specification Registry.

• Frequency:
  • Genomes: 𝑓 0.018 (313 hom., cov: 33)
  • Exomes 𝑓: 0.038 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SGCD ENST00000959782.1 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 2.15
• Publications: 0 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, STRONG Submitted by: ClinGen, PanelApp Australia
• autosomal recessive limb-girdle muscular dystrophy type 2F

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

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

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

  Inheritance: AD Classification: NO_KNOWN Submitted by: Ambry Genetics

LOC124901120 (HGNC:):

ACMG classification

Specifications for SGCD are available in the ClinGen Criteria Specification Registry and recommended for reference when assigning criteria.

Our verdict: Benign. The variant received -16 ACMG points.

• BP6: Variant 5-156326646-CTGTAATAAGCT-C is Benign according to our data. Variant chr5-156326646-CTGTAATAAGCT-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 556599.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.323 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000959782.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

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

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SGCD	ENST00000959782.1		c.-43-2887_-43-2877delTGTAATAAGCT		intron	N/A	ENSP00000629841.1
	SGCD	ENST00000517913.5	TSL:5	c.-43-2887_-43-2877delTGTAATAAGCT		intron	N/A	ENSP00000429378.1	Q92629-3
	SGCD	ENST00000435422.7	TSL:1	c.-586_-576delTGTAATAAGCT		upstream_gene	N/A	ENSP00000403003.2	Q92629-1

Frequencies

GnomAD3 genomes AF: 0.0183 AC: 2791 AN: 152126 Hom.: 317 Cov.: 33

Gnomad AFR AF: 0.00154

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0115

Gnomad ASJ AF: 0.00806

Gnomad EAS AF: 0.337

Gnomad SAS AF: 0.0742

Gnomad FIN AF: 0.0225

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00215

Gnomad OTH AF: 0.0181

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0385 AC: 1 AN: 26 Hom.: 0 AF XY: 0.0625 AC XY: 1 AN XY: 16

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.500 AC: 1 AN: 2

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 16

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 6

Other (OTH) AF: 0.00 AC: 0 AN: 2

GnomAD4 genome AF: 0.0182 AC: 2775 AN: 152242 Hom.: 313 Cov.: 33 AF XY: 0.0224 AC XY: 1668 AN XY: 74410

African (AFR) AF: 0.00154 AC: 64 AN: 41562

American (AMR) AF: 0.0113 AC: 173 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00806 AC: 28 AN: 3472

East Asian (EAS) AF: 0.336 AC: 1729 AN: 5140

South Asian (SAS) AF: 0.0740 AC: 357 AN: 4822

European-Finnish (FIN) AF: 0.0225 AC: 239 AN: 10602

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.00215 AC: 146 AN: 68028

Other (OTH) AF: 0.0175 AC: 37 AN: 2116

Alfa AF: 0.00845 Hom.: 11

Bravo AF: 0.0176

Asia WGS AF: 0.156 AC: 539 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Autosomal recessive limb-girdle muscular dystrophy type 2F (1)
-	-	1	Autosomal recessive limb-girdle muscular dystrophy type 2F;C1847667:Dilated cardiomyopathy 1L (1)
-	-	1	Dilated cardiomyopathy 1L (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.2
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: rs149976574; hg19: chr5-155753656;