rs2697782

Positions:

• chr2-232542806-G-C

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.605-76G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.333 in 1,337,110 control chromosomes in the GnomAD database, including 76,386 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.36 (9993 hom., cov: 33)
  • Exomes 𝑓: 0.33 (66393 hom.)
• Consequence: CHRNG NM_005199.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.618

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=-0.84).
• BP6: Variant 2-232542806-G-C is Benign according to our data. Variant chr2-232542806-G-C is described in ClinVar as [Benign]. Clinvar id is 1271657.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.435 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHRNG	NM_005199.5	c.605-76G>C		intron_variant		ENST00000651502.1	NP_005190.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHRNG	ENST00000651502.1	c.605-76G>C		intron_variant			NM_005199.5	ENSP00000498757.1
CHRNG	ENST00000389492.3	c.449-76G>C		intron_variant		1		ENSP00000374143.3

Frequencies

GnomAD3 genomes AF: 0.355 AC: 54026 AN: 151984 Hom.: 9980 Cov.: 33

Gnomad AFR AF: 0.440

Gnomad AMI AF: 0.337

Gnomad AMR AF: 0.253

Gnomad ASJ AF: 0.304

Gnomad EAS AF: 0.342

Gnomad SAS AF: 0.243

Gnomad FIN AF: 0.363

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.339

Gnomad OTH AF: 0.315

GnomAD4 exome AF: 0.330 AC: 391622 AN: 1185008 Hom.: 66393 AF XY: 0.327 AC XY: 195594 AN XY: 597670

Gnomad4 AFR exome AF: 0.450

Gnomad4 AMR exome AF: 0.224

Gnomad4 ASJ exome AF: 0.298

Gnomad4 EAS exome AF: 0.304

Gnomad4 SAS exome AF: 0.239

Gnomad4 FIN exome AF: 0.353

Gnomad4 NFE exome AF: 0.340

Gnomad4 OTH exome AF: 0.327

GnomAD4 genome AF: 0.356 AC: 54078 AN: 152102 Hom.: 9993 Cov.: 33 AF XY: 0.352 AC XY: 26147 AN XY: 74340

Gnomad4 AFR AF: 0.441

Gnomad4 AMR AF: 0.252

Gnomad4 ASJ AF: 0.304

Gnomad4 EAS AF: 0.342

Gnomad4 SAS AF: 0.243

Gnomad4 FIN AF: 0.363

Gnomad4 NFE AF: 0.339

Gnomad4 OTH AF: 0.312

Alfa AF: 0.156 Hom.: 312

Bravo AF: 0.352

Asia WGS AF: 0.263 AC: 912 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	Jul 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	7.6
DANN	Benign	0.66

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs2697782; hg19: chr2-233407516; COSMIC: COSV67316144; COSMIC: COSV67316144;