rs225170

Positions:

• chr4-52029884-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000232.5(SGCB):​c.244-21T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.525 in 1,589,616 control chromosomes in the GnomAD database, including 228,198 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.44 (17075 hom., cov: 32)
  • Exomes 𝑓: 0.53 (211123 hom.)
• Consequence: SGCB NM_000232.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -0.452

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 4-52029884-A-G is Benign according to our data. Variant chr4-52029884-A-G is described in ClinVar as [Benign]. Clinvar id is 255605.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-52029884-A-G is described in Lovd as [Benign]. Variant chr4-52029884-A-G is described in Lovd as [Likely_benign].
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.571 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SGCB	NM_000232.5	c.244-21T>C		intron_variant		ENST00000381431.10	NP_000223.1
SGCB	XM_047416074.1	c.34-21T>C		intron_variant			XP_047272030.1
SGCB	XM_047416075.1	c.-54-21T>C		intron_variant			XP_047272031.1
SGCB	XM_047416076.1	c.-54-21T>C		intron_variant			XP_047272032.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SGCB	ENST00000381431.10	c.244-21T>C		intron_variant		1	NM_000232.5	ENSP00000370839.6
SGCB	ENST00000506357.5	n.*26-21T>C		intron_variant		5		ENSP00000421235.1
SGCB	ENST00000514133.1	n.*39-21T>C		intron_variant		5		ENSP00000425818.1

Frequencies

GnomAD3 genomes AF: 0.437 AC: 66430 AN: 151900 Hom.: 17068 Cov.: 32

Gnomad AFR AF: 0.158

Gnomad AMI AF: 0.743

Gnomad AMR AF: 0.562

Gnomad ASJ AF: 0.473

Gnomad EAS AF: 0.347

Gnomad SAS AF: 0.356

Gnomad FIN AF: 0.491

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.575

Gnomad OTH AF: 0.498

GnomAD3 exomes AF: 0.499 AC: 124938 AN: 250610 Hom.: 33187 AF XY: 0.497 AC XY: 67273 AN XY: 135458

Gnomad AFR exome AF: 0.149

Gnomad AMR exome AF: 0.597

Gnomad ASJ exome AF: 0.487

Gnomad EAS exome AF: 0.346

Gnomad SAS exome AF: 0.355

Gnomad FIN exome AF: 0.516

Gnomad NFE exome AF: 0.577

Gnomad OTH exome AF: 0.544

GnomAD4 exome AF: 0.534 AC: 767583 AN: 1437600 Hom.: 211123 Cov.: 26 AF XY: 0.530 AC XY: 379826 AN XY: 716764

Gnomad4 AFR exome AF: 0.143

Gnomad4 AMR exome AF: 0.592

Gnomad4 ASJ exome AF: 0.481

Gnomad4 EAS exome AF: 0.346

Gnomad4 SAS exome AF: 0.357

Gnomad4 FIN exome AF: 0.521

Gnomad4 NFE exome AF: 0.568

Gnomad4 OTH exome AF: 0.503

GnomAD4 genome AF: 0.437 AC: 66474 AN: 152016 Hom.: 17075 Cov.: 32 AF XY: 0.431 AC XY: 31999 AN XY: 74268

Gnomad4 AFR AF: 0.158

Gnomad4 AMR AF: 0.562

Gnomad4 ASJ AF: 0.473

Gnomad4 EAS AF: 0.348

Gnomad4 SAS AF: 0.358

Gnomad4 FIN AF: 0.491

Gnomad4 NFE AF: 0.576

Gnomad4 OTH AF: 0.497

Alfa AF: 0.520 Hom.: 12481

Bravo AF: 0.435

Asia WGS AF: 0.362 AC: 1258 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Autosomal recessive limb-girdle muscular dystrophy type 2E Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Aug 07, 2023	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 15, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Pars Genome Lab	Jun 15, 2021	- -

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 19, 2018	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.78
DANN	Benign	0.69

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: rs225170; hg19: chr4-52896050; COSMIC: COSV67340602;