2-232545584-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_005199.5(CHRNG):c.1422C>T(p.Arg474Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.198 in 1,613,722 control chromosomes in the GnomAD database, including 32,366 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.18 ( 2590 hom., cov: 32)

Exomes 𝑓: 0.20 ( 29776 hom. )

Consequence

CHRNG
NM_005199.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -3.64

Publications

11 publications found

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:

TIGD1 (HGNC:14523): (tigger transposable element derived 1) The protein encoded by this gene belongs to the tigger subfamily of the pogo superfamily of DNA-mediated transposons in humans. These proteins are related to DNA transposons found in fungi and nematodes, and more distantly to the Tc1 and mariner transposases. They are also very similar to the major mammalian centromere protein B. The exact function of this gene is not known. [provided by RefSeq, Jul 2008]

TIGD1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.53).

BP6

Variant 2-232545584-C-T is Benign according to our data. Variant chr2-232545584-C-T is described in ClinVar as Benign. ClinVar VariationId is 194064.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-3.64 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.203 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHRNG	NM_005199.5 link	c.1422C>T	p.Arg474Arg	synonymous_variant	Exon 12 of 12	ENST00000651502.1	NP_005190.4	P07510-1A0A6F7YAP6
TIGD1	NM_145702.4 link	c.*2523G>A		3_prime_UTR_variant	Exon 1 of 1	ENST00000408957.7	NP_663748.1	Q96MW7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CHRNG	ENST00000651502.1 link	c.1422C>T	p.Arg474Arg	synonymous_variant	Exon 12 of 12		NM_005199.5	ENSP00000498757.1	P07510-1
CHRNG	ENST00000389492.3 link	c.1266C>T	p.Arg422Arg	synonymous_variant	Exon 11 of 11	1		ENSP00000374143.3	P07510-2
TIGD1	ENST00000408957.7 link	c.*2523G>A		3_prime_UTR_variant	Exon 1 of 1	6	NM_145702.4	ENSP00000386186.3	Q96MW7

Frequencies

GnomAD3 genomes

AF:

0.177

AC:

26888

AN:

152022

Hom.:

2592

Cov.:

show subpopulations

Gnomad AFR

AF:

0.121

Gnomad AMI

AF:

0.192

Gnomad AMR

AF:

0.189

Gnomad ASJ

AF:

0.249

Gnomad EAS

AF:

0.106

Gnomad SAS

AF:

0.216

Gnomad FIN

AF:

0.200

Gnomad MID

AF:

0.272

Gnomad NFE

AF:

0.203

Gnomad OTH

AF:

0.192

GnomAD2 exomes

AF:

0.187

AC:

46845

AN:

250646

AF XY:

0.191

show subpopulations

Gnomad AFR exome

AF:

0.119

Gnomad AMR exome

AF:

0.158

Gnomad ASJ exome

AF:

0.244

Gnomad EAS exome

AF:

0.107

Gnomad FIN exome

AF:

0.202

Gnomad NFE exome

AF:

0.202

Gnomad OTH exome

AF:

0.215

GnomAD4 exome

AF:

0.200

AC:

292114

AN:

1461582

Hom.:

29776

Cov.:

AF XY:

0.201

AC XY:

145796

AN XY:

727108

show subpopulations

African (AFR)

AF:

0.125

AC:

4201

AN:

33480

American (AMR)

AF:

0.160

AC:

7136

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.244

AC:

6366

AN:

26136

East Asian (EAS)

AF:

0.104

AC:

4119

AN:

39700

South Asian (SAS)

AF:

0.213

AC:

18343

AN:

86250

European-Finnish (FIN)

AF:

0.205

AC:

10909

AN:

53270

Middle Eastern (MID)

AF:

0.236

AC:

1362

AN:

5768

European-Non Finnish (NFE)

AF:

0.205

AC:

227714

AN:

1111876

Other (OTH)

AF:

0.198

AC:

11964

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

14252

28504

42757

57009

71261

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7860

15720

23580

31440

39300

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.177

AC:

26870

AN:

152140

Hom.:

2590

Cov.:

AF XY:

0.178

AC XY:

13226

AN XY:

74394

show subpopulations

African (AFR)

AF:

0.121

AC:

5006

AN:

41518

American (AMR)

AF:

0.189

AC:

2890

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.249

AC:

863

AN:

3468

East Asian (EAS)

AF:

0.106

AC:

547

AN:

5176

South Asian (SAS)

AF:

0.214

AC:

1032

AN:

4822

European-Finnish (FIN)

AF:

0.200

AC:

2115

AN:

10590

Middle Eastern (MID)

AF:

0.259

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.203

AC:

13766

AN:

67968

Other (OTH)

AF:

0.190

AC:

400

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1151

2302

3454

4605

5756

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

306

612

918

1224

1530

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.195

Hom.:

12506

Bravo

AF:

0.170

Asia WGS

AF:

0.147

AC:

512

AN:

3478

EpiCase

AF:

0.203

EpiControl

AF:

0.204

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jan 23, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Nov 10, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:2

Nov 17, 2014

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Autosomal recessive multiple pterygium syndrome

Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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. -

Lethal multiple pterygium syndrome

Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.53

CADD

Benign

0.061

(source)

DANN

Benign

0.89

PhyloP100

-3.6

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over