rs7725121

Positions:

• chr5-156326973-A-T

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The XR_007059016.1(LOC124901120):​n.234+20480T>A variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0679 in 152,408 control chromosomes in the GnomAD database, including 381 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.068 (381 hom., cov: 33)
  • Exomes 𝑓: 0.081 (0 hom.)
• Consequence: LOC124901120 XR_007059016.1 intron, non_coding_transcript
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: 2.43

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]

LOC124901120 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BP6: Variant 5-156326973-A-T is Benign according to our data. Variant chr5-156326973-A-T is described in ClinVar as [Likely_benign]. Clinvar id is 48111.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.177 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LOC124901120	XR_007059016.1	n.234+20480T>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SGCD	ENST00000435422.7	c.-260A>T		5_prime_UTR_variant	1/8	1		ENSP00000403003	A1
SGCD	ENST00000517913.5	c.-43-2561A>T		intron_variant		5		ENSP00000429378
SGCD	ENST00000524347.2	c.-303A>T		5_prime_UTR_variant, NMD_transcript_variant	1/6	5		ENSP00000430794

Frequencies

GnomAD3 genomes AF: 0.0678 AC: 10326 AN: 152228 Hom.: 381 Cov.: 33

Gnomad AFR AF: 0.0518

Gnomad AMI AF: 0.0647

Gnomad AMR AF: 0.0766

Gnomad ASJ AF: 0.0838

Gnomad EAS AF: 0.0472

Gnomad SAS AF: 0.186

Gnomad FIN AF: 0.0447

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0713

Gnomad OTH AF: 0.0764

GnomAD4 exome AF: 0.0806 AC: 5 AN: 62 Hom.: 0 Cov.: 0 AF XY: 0.0833 AC XY: 4 AN XY: 48

Gnomad4 AFR exome AF: 0.00

Gnomad4 SAS exome AF: 0.250

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0833

Gnomad4 OTH exome AF: 0.0714

GnomAD4 genome AF: 0.0679 AC: 10348 AN: 152346 Hom.: 381 Cov.: 33 AF XY: 0.0698 AC XY: 5202 AN XY: 74508

Gnomad4 AFR AF: 0.0517

Gnomad4 AMR AF: 0.0775

Gnomad4 ASJ AF: 0.0838

Gnomad4 EAS AF: 0.0475

Gnomad4 SAS AF: 0.187

Gnomad4 FIN AF: 0.0447

Gnomad4 NFE AF: 0.0713

Gnomad4 OTH AF: 0.0756

Alfa AF: 0.0703 Hom.: 43

Bravo AF: 0.0669

Asia WGS AF: 0.115 AC: 400 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Apr 20, 2012

- -

Autosomal recessive limb-girdle muscular dystrophy type 2F Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Feb 08, 2023

- -

Qualitative or quantitative defects of delta-sarcoglycan Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Limb-girdle muscular dystrophy, recessive Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Dilated cardiomyopathy 1L Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Feb 08, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	17
DANN	Benign	0.92

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs7725121; hg19: chr5-155753983;