Variant 2-232543748-C-T 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_005199.5(CHRNG):c.1035+49C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0243 in 1,144,696 control chromosomes in the GnomAD database, including 653 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.023 ( 84 hom., cov: 32)

Exomes 𝑓: 0.025 ( 569 hom. )

Consequence

CHRNG
NM_005199.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.00

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=-0.9).

BP6

Variant 2-232543748-C-T is Benign according to our data. Variant chr2-232543748-C-T is described in ClinVar as [Benign]. Clinvar id is 259664.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0918 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.1035+49C>T		intron_variant		ENST00000651502.1	NP_005190.4	P07510-1A0A6F7YAP6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHRNG	ENST00000651502.1 linkuse as main transcript	c.1035+49C>T		intron_variant			NM_005199.5	ENSP00000498757.1		P07510-1
CHRNG	ENST00000389492.3 linkuse as main transcript	c.879+49C>T		intron_variant		1		ENSP00000374143.3		P07510-2

Frequencies

GnomAD3 genomes

AF:

0.0227

AC:

3450

AN:

152158

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0119

Gnomad AMI

AF:

0.00329

Gnomad AMR

AF:

0.0415

Gnomad ASJ

AF:

0.00519

Gnomad EAS

AF:

0.0992

Gnomad SAS

AF:

0.0288

Gnomad FIN

AF:

0.0331

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0181

Gnomad OTH

AF:

0.0282

GnomAD3 exomes

AF:

0.0316

AC:

7338

AN:

232476

Hom.:

176

AF XY:

0.0299

AC XY:

3765

AN XY:

125988

show subpopulations

Gnomad AFR exome

AF:

0.0111

Gnomad AMR exome

AF:

0.0674

Gnomad ASJ exome

AF:

0.00754

Gnomad EAS exome

AF:

0.0779

Gnomad SAS exome

AF:

0.0278

Gnomad FIN exome

AF:

0.0325

Gnomad NFE exome

AF:

0.0188

Gnomad OTH exome

AF:

0.0297

GnomAD4 exome

AF:

0.0246

AC:

24393

AN:

992420

Hom.:

569

Cov.:

AF XY:

0.0245

AC XY:

12554

AN XY:

512782

show subpopulations

Gnomad4 AFR exome

AF:

0.0107

Gnomad4 AMR exome

AF:

0.0639

Gnomad4 ASJ exome

AF:

0.00695

Gnomad4 EAS exome

AF:

0.104

Gnomad4 SAS exome

AF:

0.0286

Gnomad4 FIN exome

AF:

0.0323

Gnomad4 NFE exome

AF:

0.0178

Gnomad4 OTH exome

AF:

0.0273

GnomAD4 genome

AF:

0.0227

AC:

3453

AN:

152276

Hom.:

Cov.:

AF XY:

0.0234

AC XY:

1739

AN XY:

74434

show subpopulations

Gnomad4 AFR

AF:

0.0119

Gnomad4 AMR

AF:

0.0415

Gnomad4 ASJ

AF:

0.00519

Gnomad4 EAS

AF:

0.0989

Gnomad4 SAS

AF:

0.0294

Gnomad4 FIN

AF:

0.0331

Gnomad4 NFE

AF:

0.0181

Gnomad4 OTH

AF:

0.0284

Alfa

AF:

0.0108

Hom.:

Bravo

AF:

0.0241

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 17, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

1.9

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