NM_000232.5:c.*2097T>G

Variant names:

• chr4-52021860-A-C
• rs170424
• NM_000232.5:c.*2097T>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000232.5(SGCB):​c.*2097T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.577 in 151,992 control chromosomes in the GnomAD database, including 28,291 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.58 (28291 hom., cov: 31)
  • Failed GnomAD Quality Control
• Consequence: SGCB NM_000232.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.563
• Publications: 12 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: Orphanet, Labcorp Genetics (formerly Invitae), Myriad Women’s Health, Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BP6: Variant 4-52021860-A-C is Benign according to our data. Variant chr4-52021860-A-C is described in ClinVar as Benign. ClinVar VariationId is 348860.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.715 is higher than 0.05.

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.*2097T>G		3_prime_UTR	Exon 6 of 6	NP_000223.1	Q5U0N0
	SGCB	NM_001440519.1		c.*2097T>G		3_prime_UTR	Exon 5 of 5	NP_001427448.1
	SGCB	NM_001440520.1		c.*2097T>G		3_prime_UTR	Exon 7 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.*2097T>G		3_prime_UTR	Exon 6 of 6	ENSP00000370839.6	Q16585-1
	SGCB	ENST00000899666.1		c.*2097T>G		3_prime_UTR	Exon 6 of 6	ENSP00000569725.1
	SGCB	ENST00000912466.1		c.*2097T>G		3_prime_UTR	Exon 5 of 5	ENSP00000582525.1

Frequencies

GnomAD3 genomes AF: 0.577 AC: 87670 AN: 151876 Hom.: 28279 Cov.: 31

Gnomad AFR AF: 0.275

Gnomad AMI AF: 0.763

Gnomad AMR AF: 0.703

Gnomad ASJ AF: 0.728

Gnomad EAS AF: 0.395

Gnomad SAS AF: 0.526

Gnomad FIN AF: 0.684

Gnomad MID AF: 0.790

Gnomad NFE AF: 0.721

Gnomad OTH AF: 0.644

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.577 AC: 87735 AN: 151992 Hom.: 28291 Cov.: 31 AF XY: 0.576 AC XY: 42790 AN XY: 74270

African (AFR) AF: 0.276 AC: 11444 AN: 41458

American (AMR) AF: 0.702 AC: 10717 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.728 AC: 2525 AN: 3470

East Asian (EAS) AF: 0.396 AC: 2047 AN: 5172

South Asian (SAS) AF: 0.528 AC: 2541 AN: 4814

European-Finnish (FIN) AF: 0.684 AC: 7208 AN: 10540

Middle Eastern (MID) AF: 0.779 AC: 226 AN: 290

European-Non Finnish (NFE) AF: 0.721 AC: 48981 AN: 67970

Other (OTH) AF: 0.643 AC: 1355 AN: 2108

Alfa AF: 0.693 Hom.: 42875

Bravo AF: 0.569

Asia WGS AF: 0.479 AC: 1662 AN: 3470

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Limb-girdle muscular dystrophy, recessive (1)
-	-	1	not provided (1)
-	-	1	Qualitative or quantitative defects of beta-sarcoglycan (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	7.9
DANN	Benign	0.68
PhyloP100		0.56
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs170424; hg19: chr4-52888026;