rs886043197

Positions:

• chr4-52028925-CAA-C
• chr4-52028925-CA-C
• chr4-52028925-C-CA

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_000232.5(SGCB):​c.430-6_430-5delTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SGCB NM_000232.5 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.09

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SGCB	NM_000232.5	c.430-6_430-5delTT		splice_region_variant, intron_variant		ENST00000381431.10	NP_000223.1
SGCB	XM_047416074.1	c.220-6_220-5delTT		splice_region_variant, intron_variant			XP_047272030.1
SGCB	XM_047416075.1	c.133-6_133-5delTT		splice_region_variant, intron_variant			XP_047272031.1
SGCB	XM_047416076.1	c.133-6_133-5delTT		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.430-6_430-5delTT		splice_region_variant, intron_variant		1	NM_000232.5	ENSP00000370839.6
SGCB	ENST00000506357.5	n.*212-6_*212-5delTT		splice_region_variant, intron_variant		5		ENSP00000421235.1
SGCB	ENST00000514133.1	n.*225-6_*225-5delTT		splice_region_variant, intron_variant		5		ENSP00000425818.1

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.19		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;