Variant rs225170 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.452

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 255605.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-52029884-A-G is described in Lovd as [Benign]. Variant chr4-52029884-A-G is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.571 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
SGCB	NM_000232.5 linkuse as main transcript	c.244-21T>C	intron_variant	ENST00000381431.10
SGCB	XM_047416074.1 linkuse as main transcript	c.34-21T>C	intron_variant
SGCB	XM_047416075.1 linkuse as main transcript	c.-54-21T>C	intron_variant
SGCB	XM_047416076.1 linkuse as main transcript	c.-54-21T>C	intron_variant

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris	UniProt
SGCB	ENST00000381431.10 linkuse as main transcript	c.244-21T>C	intron_variant	1	NM_000232.5	P1	Q16585-1
SGCB	ENST00000506357.5 linkuse as main transcript	c.*26-21T>C	intron_variant, NMD_transcript_variant	5
SGCB	ENST00000514133.1 linkuse as main transcript	c.*39-21T>C	intron_variant, NMD_transcript_variant	5

Frequencies

GnomAD3 genomes

AF:

0.437

AC:

66430

AN:

151900

Hom.:

17068

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.499

AC:

124938

AN:

250610

Hom.:

33187

AF XY:

0.497

AC XY:

67273

AN XY:

135458

show subpopulations

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 SAS exome

AF:

0.355

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.:

AF XY:

0.530

AC XY:

379826

AN XY:

716764

show subpopulations

Gnomad4 AFR exome

AF:

0.143

Gnomad4 AMR exome

AF:

0.592

Gnomad4 ASJ exome

AF:

0.481

Gnomad4 EAS exome

AF:

0.346

Gnomad4 SAS exome

AF:

0.357

Gnomad4 FIN exome

AF:

0.521

Gnomad4 NFE exome

AF:

0.568

Gnomad4 OTH exome

AF:

0.503

GnomAD4 genome

AF:

0.437

AC:

66474

AN:

152016

Hom.:

17075

Cov.:

AF XY:

0.431

AC XY:

31999

AN XY:

74268

show subpopulations

Gnomad4 AFR

AF:

0.158

Gnomad4 AMR

AF:

0.562

Gnomad4 ASJ

AF:

0.473

Gnomad4 EAS

AF:

0.348

Gnomad4 SAS

AF:

0.358

Gnomad4 FIN

AF:

0.491

Gnomad4 NFE

AF:

0.576

Gnomad4 OTH

AF:

0.497

Alfa

AF:

0.520

Hom.:

12481

Bravo

AF:

0.435

Asia WGS

AF:

0.362

AC:

1258

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Autosomal recessive limb-girdle muscular dystrophy type 2E

Benign:3

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 15, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Aug 07, 2023	- -
Benign, criteria provided, single submitter	clinical testing	Pars Genome Lab	Jun 15, 2021	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 19, 2018

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

0.78

DANN

Benign

0.69

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over