rs114128937

Variant names:

• chr5-156326739-C-A
• rs114128937
• ENST00000517913.5:c.-43-2795C>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The XR_007059016.1(LOC124901120):​n.234+20714G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0129 in 152,528 control chromosomes in the GnomAD database, including 22 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.013 (22 hom., cov: 33)
  • Exomes 𝑓: 0.0085 (0 hom.)
• Consequence: LOC124901120 XR_007059016.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.965
• 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

LOC124901120 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BP6: Variant 5-156326739-C-A is Benign according to our data. Variant chr5-156326739-C-A is described in ClinVar as [Benign]. Clinvar id is 1183373.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.0129 (1972/152292) while in subpopulation SAS AF = 0.0184 (89/4828). AF 95% confidence interval is 0.0153. There are 22 homozygotes in GnomAd4. There are 997 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 22 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SGCD	XM_017009724.2	c.-43-2795C>A		intron_variant	Intron 2 of 9		XP_016865213.1
SGCD	XM_047417518.1	c.-43-2795C>A		intron_variant	Intron 4 of 11		XP_047273474.1
SGCD	XM_047417519.1	c.-43-2795C>A		intron_variant	Intron 3 of 10		XP_047273475.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SGCD	ENST00000517913.5	c.-43-2795C>A		intron_variant	Intron 3 of 9	5		ENSP00000429378.1
SGCD	ENST00000435422.7	c.-494C>A		upstream_gene_variant		1		ENSP00000403003.2
SGCD	ENST00000524347.2	n.-537C>A		upstream_gene_variant		5		ENSP00000430794.1

Frequencies

GnomAD3 genomes AF: 0.0129 AC: 1959 AN: 152174 Hom.: 20 Cov.: 33

Gnomad AFR AF: 0.0122

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0115

Gnomad ASJ AF: 0.0199

Gnomad EAS AF: 0.0141

Gnomad SAS AF: 0.0178

Gnomad FIN AF: 0.0142

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0127

Gnomad OTH AF: 0.0124

GnomAD4 exome AF: 0.00847 AC: 2 AN: 236 Hom.: 0 Cov.: 0 AF XY: 0.0118 AC XY: 2 AN XY: 170

African (AFR) AF: 0.00 AC: 0 AN: 4

American (AMR) AF: 0.00 AC: 0 AN: 4

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 4

East Asian (EAS) AF: 0.00 AC: 0 AN: 6

South Asian (SAS) AF: 0.00 AC: 0 AN: 6

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 60

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2

European-Non Finnish (NFE) AF: 0.0145 AC: 2 AN: 138

Other (OTH) AF: 0.00 AC: 0 AN: 12

GnomAD4 genome AF: 0.0129 AC: 1972 AN: 152292 Hom.: 22 Cov.: 33 AF XY: 0.0134 AC XY: 997 AN XY: 74458

African (AFR) AF: 0.0124 AC: 517 AN: 41560

American (AMR) AF: 0.0115 AC: 176 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0199 AC: 69 AN: 3470

East Asian (EAS) AF: 0.0141 AC: 73 AN: 5182

South Asian (SAS) AF: 0.0184 AC: 89 AN: 4828

European-Finnish (FIN) AF: 0.0142 AC: 151 AN: 10600

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.0127 AC: 865 AN: 68030

Other (OTH) AF: 0.0123 AC: 26 AN: 2116

Alfa AF: 0.0129 Hom.: 2

Bravo AF: 0.0123

Asia WGS AF: 0.0200 AC: 71 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	15
DANN	Benign	0.81
PhyloP100		0.96
PromoterAI		0.0082	Neutral
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs114128937; hg19: chr5-155753749;