2-232542410-C-T

Position:

chr2-232542410-C-T

Variant summary

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

The NM_005199.5(CHRNG):c.507-13C>T variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.23 in 1,595,044 control chromosomes in the GnomAD database, including 44,308 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.20 ( 3377 hom., cov: 32)

Exomes 𝑓: 0.23 ( 40931 hom. )

Consequence

CHRNG
NM_005199.5 splice_polypyrimidine_tract, intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: -0.533

Variant links:

Genes affected

CHRNG (HGNC:1967): (cholinergic receptor nicotinic gamma subunit) The mammalian muscle-type acetylcholine receptor is a transmembrane pentameric glycoprotein with two alpha subunits, one beta, one delta, and one epsilon (in adult skeletal muscle) or gamma (in fetal and denervated muscle) subunit. This gene, which encodes the gamma subunit, is expressed prior to the thirty-third week of gestation in humans. The gamma subunit of the acetylcholine receptor plays a role in neuromuscular organogenesis and ligand binding and disruption of gamma subunit expression prevents the correct localization of the receptor in cell membranes. Mutations in this gene cause Escobar syndrome and a lethal form of multiple pterygium syndrome. Muscle-type acetylcholine receptor is the major antigen in the autoimmune disease myasthenia gravis.[provided by RefSeq, Sep 2009]

CHRNG 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=-0.88).

BP6

Variant 2-232542410-C-T is Benign according to our data. Variant chr2-232542410-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 198182.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-232542410-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.298 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHRNG	NM_005199.5 linkuse as main transcript	c.507-13C>T		splice_polypyrimidine_tract_variant, intron_variant		ENST00000651502.1	NP_005190.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHRNG	ENST00000651502.1 linkuse as main transcript	c.507-13C>T		splice_polypyrimidine_tract_variant, intron_variant			NM_005199.5	ENSP00000498757	P1	P07510-1
CHRNG	ENST00000389492.3 linkuse as main transcript	c.351-13C>T		splice_polypyrimidine_tract_variant, intron_variant		1		ENSP00000374143		P07510-2

Frequencies

GnomAD3 genomes

AF:

0.200

AC:

30362

AN:

151996

Hom.:

3378

Cov.:

show subpopulations

Gnomad AFR

AF:

0.128

Gnomad AMI

AF:

0.116

Gnomad AMR

AF:

0.132

Gnomad ASJ

AF:

0.187

Gnomad EAS

AF:

0.310

Gnomad SAS

AF:

0.153

Gnomad FIN

AF:

0.287

Gnomad MID

AF:

0.115

Gnomad NFE

AF:

0.243

Gnomad OTH

AF:

0.171

GnomAD3 exomes

AF:

0.210

AC:

52136

AN:

247816

Hom.:

5985

AF XY:

0.211

AC XY:

28277

AN XY:

133808

show subpopulations

Gnomad AFR exome

AF:

0.129

Gnomad AMR exome

AF:

0.108

Gnomad ASJ exome

AF:

0.186

Gnomad EAS exome

AF:

0.299

Gnomad SAS exome

AF:

0.155

Gnomad FIN exome

AF:

0.273

Gnomad NFE exome

AF:

0.245

Gnomad OTH exome

AF:

0.194

GnomAD4 exome

AF:

0.233

AC:

336777

AN:

1442930

Hom.:

40931

Cov.:

AF XY:

0.231

AC XY:

166278

AN XY:

718788

show subpopulations

Gnomad4 AFR exome

AF:

0.131

Gnomad4 AMR exome

AF:

0.111

Gnomad4 ASJ exome

AF:

0.185

Gnomad4 EAS exome

AF:

0.267

Gnomad4 SAS exome

AF:

0.154

Gnomad4 FIN exome

AF:

0.275

Gnomad4 NFE exome

AF:

0.247

Gnomad4 OTH exome

AF:

0.220

GnomAD4 genome

AF:

0.200

AC:

30371

AN:

152114

Hom.:

3377

Cov.:

AF XY:

0.200

AC XY:

14872

AN XY:

74352

show subpopulations

Gnomad4 AFR

AF:

0.128

Gnomad4 AMR

AF:

0.132

Gnomad4 ASJ

AF:

0.187

Gnomad4 EAS

AF:

0.311

Gnomad4 SAS

AF:

0.154

Gnomad4 FIN

AF:

0.287

Gnomad4 NFE

AF:

0.243

Gnomad4 OTH

AF:

0.169

Alfa

AF:

0.219

Hom.:

4474

Bravo

AF:

0.186

Asia WGS

AF:

0.170

AC:

589

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Nov 17, 2014	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	Feb 24, 2016	- -

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Autosomal recessive multiple pterygium syndrome

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Lethal multiple pterygium syndrome

Benign:1

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 benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

4.4

DANN

Benign

0.55

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