rs1553940969

Variant names:

• chr4-52038263-C-A
• rs1553940969
• NM_000232.5:c.-4G>T

Your query was ambiguous. Multiple possible variants found:

• chr4-52038263-C-A
• chr4-52038263-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_000232.5(SGCB):​c.-4G>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000262 in 1,144,226 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000026 (0 hom.)
• Consequence: SGCB NM_000232.5 5_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.00100
• 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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000232.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SGCB	NM_000232.5	MANE Select	c.-4G>T		5_prime_UTR	Exon 1 of 6	NP_000223.1
	SGCB	NM_001440519.1		c.-4G>T		5_prime_UTR	Exon 1 of 5	NP_001427448.1
	SGCB	NM_001440520.1		c.-411G>T		5_prime_UTR	Exon 1 of 7	NP_001427449.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SGCB	ENST00000381431.10	TSL:1 MANE Select	c.-4G>T		5_prime_UTR	Exon 1 of 6	ENSP00000370839.6
	SGCB	ENST00000899666.1		c.-4G>T		5_prime_UTR	Exon 1 of 6	ENSP00000569725.1
	SGCB	ENST00000912466.1		c.-4G>T		5_prime_UTR	Exon 1 of 5	ENSP00000582525.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000262 AC: 3 AN: 1144226 Hom.: 0 Cov.: 31 AF XY: 0.00000181 AC XY: 1 AN XY: 553252

African (AFR) AF: 0.00 AC: 0 AN: 23842

American (AMR) AF: 0.00 AC: 0 AN: 17222

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17240

East Asian (EAS) AF: 0.00 AC: 0 AN: 25566

South Asian (SAS) AF: 0.00 AC: 0 AN: 35680

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 24004

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3124

European-Non Finnish (NFE) AF: 0.00000315 AC: 3 AN: 951864

Other (OTH) AF: 0.00 AC: 0 AN: 45684

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	18
DANN	Benign	0.89
PhyloP100		0.0010
PromoterAI		0.13	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.26		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.26		Position offset: 2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1553940969; hg19: chr4-52904429;