rs115928999

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

This summary comes from the ClinGen Evidence Repository: The NM_000232.5: c.92G>T variant in SGCB is a missense variant predicted to cause substitution of serine by isoleucine at amino acid 31 (p.Ser31Ile). The filtering allele frequency of this variant is 0.007653 in the African/African American population in gnomAD v3.1.2 (the lower threshold of the 95% CI of 347/41414 genome chromosomes), which is higher than the LGMD VCEP threshold (>0.002) for BA1 and therefore meets this criterion (BA1). The computational predictor REVEL gives a score of 0.18, which is above the LGMD VCEP threshold predicting a benign impact on sarcoglycan β function (<0.1; BP4 not met). In summary, this variant meets the criteria to be classified as Benign for autosomal recessive limb girdle muscular dystrophy based on the ACMG/AMP criteria applied, as specified by the ClinGen LGMD VCEP (LGMD VCEP specifications version 1.0.0; 01/09/2025): BA1. LINK:https://erepo.genome.network/evrepo/ui/classification/CA145911/MONDO:0015152/184

Frequency

Genomes: 𝑓 0.0024 ( 2 hom., cov: 32)

Exomes 𝑓: 0.00022 ( 0 hom. )

Consequence

SGCB
NM_001440520.1 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Benign reviewed by expert panel U:1B:6

Conservation

PhyloP100: 0.805

Publications

2 publications found

Variant links:

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

SGCB links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BA1

For more information check the summary or visit ClinGen Evidence Repository.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001440520.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
SGCB	NM_000232.5	MANE Select	c.92G>T	p.Ser31Ile	missense	Exon 2 of 6	NP_000223.1
SGCB	NM_001440520.1		c.-316G>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 7	NP_001427449.1
SGCB	NM_001440520.1		c.-316G>T		5_prime_UTR	Exon 2 of 7	NP_001427449.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
SGCB	ENST00000381431.10	TSL:1 MANE Select	c.92G>T	p.Ser31Ile	missense	Exon 2 of 6	ENSP00000370839.6
SGCB	ENST00000899666.1		c.92G>T	p.Ser31Ile	missense	Exon 2 of 6	ENSP00000569725.1
SGCB	ENST00000912466.1		c.92G>T	p.Ser31Ile	missense	Exon 2 of 5	ENSP00000582525.1

Frequencies

GnomAD3 genomes

AF:

0.00242

AC:

368

AN:

152170

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00838

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00118

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:

0.0000147

Gnomad OTH

AF:

0.000956

GnomAD2 exomes

AF:

0.000497

AC:

125

AN:

251468

AF XY:

0.000383

show subpopulations

Gnomad AFR exome

AF:

0.00701

Gnomad AMR exome

AF:

0.000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000223

AC:

326

AN:

1461660

Hom.:

Cov.:

AF XY:

0.000165

AC XY:

120

AN XY:

727140

show subpopulations

African (AFR)

AF:

0.00806

AC:

270

AN:

33478

American (AMR)

AF:

0.000470

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26130

East Asian (EAS)

AF:

0.00

AC:

AN:

39682

South Asian (SAS)

AF:

0.00

AC:

AN:

86250

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53414

Middle Eastern (MID)

AF:

0.00104

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00000540

AC:

AN:

1111826

Other (OTH)

AF:

0.000381

AC:

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

100

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00242

AC:

369

AN:

152288

Hom.:

Cov.:

AF XY:

0.00234

AC XY:

174

AN XY:

74476

show subpopulations

African (AFR)

AF:

0.00840

AC:

349

AN:

41536

American (AMR)

AF:

0.00111

AC:

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68018

Other (OTH)

AF:

0.000946

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

104

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000404

Hom.:

Bravo

AF:

0.00249

ESP6500AA

AF:

0.00590

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000626

AC:

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:reviewed by expert panel

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

not specified (2)

Autosomal recessive limb-girdle muscular dystrophy (1)

Autosomal recessive limb-girdle muscular dystrophy type 2E (1)

Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.26

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.38

Eigen

Benign

-0.86

Eigen_PC

Benign

-0.77

FATHMM_MKL

Benign

0.39

LIST_S2

Benign

0.77

M_CAP

Benign

0.060

MetaRNN

Benign

0.0080

MetaSVM

Benign

-0.59

MutationAssessor

Benign

0.55

PhyloP100

0.81

PrimateAI

Uncertain

0.63

PROVEAN

Benign

-1.2

REVEL

Benign

0.18

Sift

Benign

0.11

Sift4G

Benign

0.13

Polyphen

0.0060

Vest4

0.22

MVP

0.68

MPC

0.089

ClinPred

0.0079

GERP RS

4.1

Varity_R

0.058

gMVP

0.57

Mutation Taster

=89/11

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over