chr4-52028925-CAA-C

Variant names:

• chr4-52028925-CAA-C
• rs762831481
• NM_000232.5:c.430-6_430-5delTT

Variant summary

Our verdict is Uncertain significance. The variant received 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
• Publications: 0 publications found

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]

SGCB Gene-Disease associations (from GenCC):

• autosomal recessive limb-girdle muscular dystrophy

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• autosomal recessive limb-girdle muscular dystrophy type 2E

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, Myriad Women’s Health, Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SGCB	NM_000232.5	c.430-6_430-5delTT		splice_region_variant, intron_variant	Intron 3 of 5	ENST00000381431.10	NP_000223.1
SGCB	NM_001440519.1	c.220-6_220-5delTT		splice_region_variant, intron_variant	Intron 2 of 4		NP_001427448.1
SGCB	NM_001440520.1	c.133-6_133-5delTT		splice_region_variant, intron_variant	Intron 4 of 6		NP_001427449.1
SGCB	XM_047416076.1	c.133-6_133-5delTT		splice_region_variant, intron_variant	Intron 2 of 4		XP_047272032.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SGCB	ENST00000381431.10	c.430-6_430-5delTT		splice_region_variant, intron_variant	Intron 3 of 5	1	NM_000232.5	ENSP00000370839.6
SGCB	ENST00000506357.5	n.*212-6_*212-5delTT		splice_region_variant, intron_variant	Intron 4 of 4	5		ENSP00000421235.1
SGCB	ENST00000514133.1	n.*225-6_*225-5delTT		splice_region_variant, intron_variant	Intron 3 of 3	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

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.1

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

Other links and lift over

dbSNP: rs762831481; hg19: chr4-52895091;