4-52020914-T-C

Position:

• chr4-52020914-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_000232.5(SGCB):​c.*3043A>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 0.00439 in 152,682 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0044 (6 hom., cov: 32)
  • Exomes 𝑓: 0.0028 (0 hom.)
• Consequence: SGCB NM_000232.5 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.68

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 4-52020914-T-C is Benign according to our data. Variant chr4-52020914-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 902044.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00439 (669/152326) while in subpopulation NFE AF= 0.00676 (460/68034). AF 95% confidence interval is 0.00625. There are 6 homozygotes in gnomad4. There are 316 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SGCB	NM_000232.5	c.*3043A>G		3_prime_UTR_variant	6/6	ENST00000381431.10	NP_000223.1
SGCB	XM_047416074.1	c.*3043A>G		3_prime_UTR_variant	5/5		XP_047272030.1
SGCB	XM_047416075.1	c.*3043A>G		3_prime_UTR_variant	5/5		XP_047272031.1
SGCB	XM_047416076.1	c.*3043A>G		3_prime_UTR_variant	5/5		XP_047272032.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SGCB	ENST00000381431.10	c.*3043A>G		3_prime_UTR_variant	6/6	1	NM_000232.5	ENSP00000370839	P1

Frequencies

GnomAD3 genomes AF: 0.00440 AC: 670 AN: 152208 Hom.: 6 Cov.: 32

Gnomad AFR AF: 0.00135

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00445

Gnomad ASJ AF: 0.0133

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00207

Gnomad FIN AF: 0.000565

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.00676

Gnomad OTH AF: 0.00813

GnomAD4 exome AF: 0.00281 AC: 1 AN: 356 Hom.: 0 Cov.: 0 AF XY: 0.00459 AC XY: 1 AN XY: 218

Gnomad4 FIN exome AF: 0.00286

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.00439 AC: 669 AN: 152326 Hom.: 6 Cov.: 32 AF XY: 0.00424 AC XY: 316 AN XY: 74492

Gnomad4 AFR AF: 0.00135

Gnomad4 AMR AF: 0.00445

Gnomad4 ASJ AF: 0.0133

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00207

Gnomad4 FIN AF: 0.000565

Gnomad4 NFE AF: 0.00676

Gnomad4 OTH AF: 0.00805

Alfa AF: 0.00521 Hom.: 0

Bravo AF: 0.00437

Asia WGS AF: 0.00202 AC: 8 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Qualitative or quantitative defects of beta-sarcoglycan Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -

not provided Benign:1

Likely benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.28
DANN	Benign	0.63

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

LitVar

Other links and lift over

dbSNP: rs73246100; hg19: chr4-52887080;