4-52021860-A-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000232.5(SGCB):c.*2097T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.577 in 151,992 control chromosomes in the GnomAD database, including 28,291 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.58 (28291 hom., cov: 31)
  • Failed GnomAD Quality Control
• Consequence: SGCB NM_000232.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 0.563

Genes affected

SGCB (HGNC:10806): (sarcoglycan beta) This gene encodes a member of the sarcoglycan family. Sarcoglycans are transmembrane components in the dystrophin-glycoprotein complex which help stabilize the muscle fiber membranes and link the muscle cytoskeleton to the extracellular matrix. Mutations in this gene have been associated with limb-girdle muscular dystrophy.[provided by RefSeq, Oct 2008]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BP6: Variant 4-52021860-A-C is Benign according to our data. Variant chr4-52021860-A-C is described in ClinVar as [Benign]. Clinvar id is 348860.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-52021860-A-C is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.715 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SGCB	NM_000232.5	c.*2097T>G		3_prime_UTR_variant	6/6	ENST00000381431.10
SGCB	XM_047416074.1	c.*2097T>G		3_prime_UTR_variant	5/5
SGCB	XM_047416075.1	c.*2097T>G		3_prime_UTR_variant	5/5
SGCB	XM_047416076.1	c.*2097T>G		3_prime_UTR_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SGCB	ENST00000381431.10	c.*2097T>G		3_prime_UTR_variant	6/6	1	NM_000232.5	P1

Frequencies

GnomAD3 genomes AF: 0.577 AC: 87670 AN: 151876 Hom.: 28279 Cov.: 31

Gnomad AFR AF: 0.275

Gnomad AMI AF: 0.763

Gnomad AMR AF: 0.703

Gnomad ASJ AF: 0.728

Gnomad EAS AF: 0.395

Gnomad SAS AF: 0.526

Gnomad FIN AF: 0.684

Gnomad MID AF: 0.790

Gnomad NFE AF: 0.721

Gnomad OTH AF: 0.644

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.577 AC: 87735 AN: 151992 Hom.: 28291 Cov.: 31 AF XY: 0.576 AC XY: 42790 AN XY: 74270

Gnomad4 AFR AF: 0.276

Gnomad4 AMR AF: 0.702

Gnomad4 ASJ AF: 0.728

Gnomad4 EAS AF: 0.396

Gnomad4 SAS AF: 0.528

Gnomad4 FIN AF: 0.684

Gnomad4 NFE AF: 0.721

Gnomad4 OTH AF: 0.643

Alfa AF: 0.700 Hom.: 35633

Bravo AF: 0.569

Asia WGS AF: 0.479 AC: 1662 AN: 3470

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

Submissions by phenotype

Qualitative or quantitative defects of beta-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

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
Cadd	Benign	7.9
Dann	Benign	0.68

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: rs170424; hg19: chr4-52888026;