NM_000232.5:c.244-21T>C

Variant names:

• chr4-52029884-A-G
• rs225170
• NM_000232.5:c.244-21T>C

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.244-21T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.525 in 1,589,616 control chromosomes in the GnomAD database, including 228,198 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.44 (17075 hom., cov: 32)
  • Exomes 𝑓: 0.53 (211123 hom.)
• Consequence: SGCB NM_000232.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -0.452
• Publications: 10 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 4-52029884-A-G is Benign according to our data. Variant chr4-52029884-A-G is described in ClinVar as Benign. ClinVar VariationId is 255605.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.571 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SGCB	NM_000232.5	MANE Select	c.244-21T>C		intron	N/A	NP_000223.1
	SGCB	NM_001440519.1		c.34-21T>C		intron	N/A	NP_001427448.1
	SGCB	NM_001440520.1		c.-54-21T>C		intron	N/A	NP_001427449.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SGCB	ENST00000381431.10	TSL:1 MANE Select	c.244-21T>C		intron	N/A	ENSP00000370839.6
	SGCB	ENST00000899666.1		c.244-21T>C		intron	N/A	ENSP00000569725.1
	SGCB	ENST00000912466.1		c.244-21T>C		intron	N/A	ENSP00000582525.1

Frequencies

GnomAD3 genomes AF: 0.437 AC: 66430 AN: 151900 Hom.: 17068 Cov.: 32

Gnomad AFR AF: 0.158

Gnomad AMI AF: 0.743

Gnomad AMR AF: 0.562

Gnomad ASJ AF: 0.473

Gnomad EAS AF: 0.347

Gnomad SAS AF: 0.356

Gnomad FIN AF: 0.491

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.575

Gnomad OTH AF: 0.498

GnomAD2 exomes AF: 0.499 AC: 124938 AN: 250610 AF XY: 0.497

Gnomad AFR exome AF: 0.149

Gnomad AMR exome AF: 0.597

Gnomad ASJ exome AF: 0.487

Gnomad EAS exome AF: 0.346

Gnomad FIN exome AF: 0.516

Gnomad NFE exome AF: 0.577

Gnomad OTH exome AF: 0.544

GnomAD4 exome AF: 0.534 AC: 767583 AN: 1437600 Hom.: 211123 Cov.: 26 AF XY: 0.530 AC XY: 379826 AN XY: 716764

African (AFR) AF: 0.143 AC: 4730 AN: 33062

American (AMR) AF: 0.592 AC: 26450 AN: 44666

Ashkenazi Jewish (ASJ) AF: 0.481 AC: 12493 AN: 25972

East Asian (EAS) AF: 0.346 AC: 13703 AN: 39572

South Asian (SAS) AF: 0.357 AC: 30598 AN: 85760

European-Finnish (FIN) AF: 0.521 AC: 27770 AN: 53306

Middle Eastern (MID) AF: 0.510 AC: 2920 AN: 5720

European-Non Finnish (NFE) AF: 0.568 AC: 619003 AN: 1090058

Other (OTH) AF: 0.503 AC: 29916 AN: 59484

GnomAD4 genome AF: 0.437 AC: 66474 AN: 152016 Hom.: 17075 Cov.: 32 AF XY: 0.431 AC XY: 31999 AN XY: 74268

African (AFR) AF: 0.158 AC: 6566 AN: 41484

American (AMR) AF: 0.562 AC: 8582 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.473 AC: 1643 AN: 3472

East Asian (EAS) AF: 0.348 AC: 1794 AN: 5162

South Asian (SAS) AF: 0.358 AC: 1724 AN: 4822

European-Finnish (FIN) AF: 0.491 AC: 5158 AN: 10508

Middle Eastern (MID) AF: 0.537 AC: 158 AN: 294

European-Non Finnish (NFE) AF: 0.576 AC: 39128 AN: 67988

Other (OTH) AF: 0.497 AC: 1045 AN: 2104

Alfa AF: 0.517 Hom.: 16997

Bravo AF: 0.435

Asia WGS AF: 0.362 AC: 1258 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	Autosomal recessive limb-girdle muscular dystrophy type 2E (3)
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.78
DANN	Benign	0.69
PhyloP100		-0.45
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: rs225170; hg19: chr4-52896050; COSMIC: COSV67340602;