2-232543529-C-G

Position:

• chr2-232543529-C-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_005199.5(CHRNG):​c.921-56C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.835 in 1,310,424 control chromosomes in the GnomAD database, including 457,526 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.83 (52915 hom., cov: 29)
  • Exomes 𝑓: 0.83 (404611 hom.)
• Consequence: CHRNG NM_005199.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.222

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 2-232543529-C-G is Benign according to our data. Variant chr2-232543529-C-G is described in ClinVar as [Benign]. Clinvar id is 1282133.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.95 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHRNG	NM_005199.5	c.921-56C>G		intron_variant		ENST00000651502.1	NP_005190.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHRNG	ENST00000651502.1	c.921-56C>G		intron_variant			NM_005199.5	ENSP00000498757	P1
CHRNG	ENST00000389492.3	c.765-56C>G		intron_variant		1		ENSP00000374143

Frequencies

GnomAD3 genomes AF: 0.834 AC: 126467 AN: 151714 Hom.: 52869 Cov.: 29

Gnomad AFR AF: 0.821

Gnomad AMI AF: 0.811

Gnomad AMR AF: 0.863

Gnomad ASJ AF: 0.893

Gnomad EAS AF: 0.973

Gnomad SAS AF: 0.870

Gnomad FIN AF: 0.827

Gnomad MID AF: 0.858

Gnomad NFE AF: 0.820

Gnomad OTH AF: 0.832

GnomAD4 exome AF: 0.835 AC: 967246 AN: 1158592 Hom.: 404611 Cov.: 16 AF XY: 0.836 AC XY: 492267 AN XY: 589058

Gnomad4 AFR exome AF: 0.823

Gnomad4 AMR exome AF: 0.913

Gnomad4 ASJ exome AF: 0.892

Gnomad4 EAS exome AF: 0.965

Gnomad4 SAS exome AF: 0.860

Gnomad4 FIN exome AF: 0.822

Gnomad4 NFE exome AF: 0.822

Gnomad4 OTH exome AF: 0.845

GnomAD4 genome AF: 0.834 AC: 126570 AN: 151832 Hom.: 52915 Cov.: 29 AF XY: 0.835 AC XY: 61984 AN XY: 74198

Gnomad4 AFR AF: 0.821

Gnomad4 AMR AF: 0.863

Gnomad4 ASJ AF: 0.893

Gnomad4 EAS AF: 0.973

Gnomad4 SAS AF: 0.869

Gnomad4 FIN AF: 0.827

Gnomad4 NFE AF: 0.820

Gnomad4 OTH AF: 0.833

Alfa AF: 0.825 Hom.: 6457

Bravo AF: 0.838

Asia WGS AF: 0.906 AC: 3149 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 10, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.6
DANN	Benign	0.76

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: rs2573206; hg19: chr2-233408239;