4-52028925-CAA-CAAA

Position:

• chr4-52028925-CAA-CAAA

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP6

The NM_000232.5(SGCB):​c.430-5dupT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000643 in 1,601,472 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.000033 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000068 (0 hom.)
• Consequence: SGCB NM_000232.5 splice_region, intron
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:2 B:2
• Conservation: PhyloP100: 1.54

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 4-52028925-C-CA is Benign according to our data. Variant chr4-52028925-C-CA is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 285749.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=2, Benign=1}.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SGCB	NM_000232.5	c.430-5dupT		splice_region_variant, intron_variant		ENST00000381431.10	NP_000223.1
SGCB	XM_047416074.1	c.220-5dupT		splice_region_variant, intron_variant			XP_047272030.1
SGCB	XM_047416075.1	c.133-5dupT		splice_region_variant, intron_variant			XP_047272031.1
SGCB	XM_047416076.1	c.133-5dupT		splice_region_variant, intron_variant			XP_047272032.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SGCB	ENST00000381431.10	c.430-5dupT		splice_region_variant, intron_variant		1	NM_000232.5	ENSP00000370839.6
SGCB	ENST00000506357.5	n.*212-5dupT		splice_region_variant, intron_variant		5		ENSP00000421235.1
SGCB	ENST00000514133.1	n.*225-5dupT		splice_region_variant, intron_variant		5		ENSP00000425818.1

Frequencies

GnomAD3 genomes AF: 0.0000330 AC: 5 AN: 151396 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000243

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000659

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000295

Gnomad OTH AF: 0.000480

GnomAD4 exome AF: 0.0000676 AC: 98 AN: 1450076 Hom.: 0 Cov.: 29 AF XY: 0.0000554 AC XY: 40 AN XY: 722086

Gnomad4 AFR exome AF: 0.000181

Gnomad4 AMR exome AF: 0.000158

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000253

Gnomad4 SAS exome AF: 0.0000467

Gnomad4 FIN exome AF: 0.0000376

Gnomad4 NFE exome AF: 0.0000662

Gnomad4 OTH exome AF: 0.0000834

GnomAD4 genome AF: 0.0000330 AC: 5 AN: 151396 Hom.: 0 Cov.: 33 AF XY: 0.0000406 AC XY: 3 AN XY: 73916

Gnomad4 AFR AF: 0.0000243

Gnomad4 AMR AF: 0.0000659

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000295

Gnomad4 OTH AF: 0.000480

Bravo AF: 0.0000529

EpiCase AF: 0.0000549

EpiControl AF: 0.0000597

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:2 Benign:2

Revision: criteria provided, conflicting classifications

Submissions by phenotype

not provided Uncertain:2 Benign:1

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 04, 2019	This variant is associated with the following publications: (PMID: 30564623) -
Uncertain significance, criteria provided, single submitter	clinical testing	Athena Diagnostics	Jul 10, 2018	- -
Uncertain significance, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jan 25, 2016	- -

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

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 17, 2024

- -

Computational scores

Source: dbNSFP v4.3

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: rs762831481; hg19: chr4-52895091;