2-232539880-G-C

Position:

• chr2-232539880-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.55+78G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.345 in 1,608,468 control chromosomes in the GnomAD database, including 99,231 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.31 (8006 hom., cov: 33)
  • Exomes 𝑓: 0.35 (91225 hom.)
• Consequence: CHRNG NM_005199.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.59

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=-0.91).
• BP6: Variant 2-232539880-G-C is Benign according to our data. Variant chr2-232539880-G-C is described in ClinVar as [Benign]. Clinvar id is 1290181.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.437 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHRNG	NM_005199.5	c.55+78G>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.55+78G>C		intron_variant			NM_005199.5	ENSP00000498757	P1
CHRNG	ENST00000389492.3	c.55+78G>C		intron_variant		1		ENSP00000374143
CHRNG	ENST00000485094.1	n.76+78G>C		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.310 AC: 47073 AN: 151940 Hom.: 7988 Cov.: 33

Gnomad AFR AF: 0.181

Gnomad AMI AF: 0.400

Gnomad AMR AF: 0.445

Gnomad ASJ AF: 0.362

Gnomad EAS AF: 0.444

Gnomad SAS AF: 0.405

Gnomad FIN AF: 0.297

Gnomad MID AF: 0.329

Gnomad NFE AF: 0.339

Gnomad OTH AF: 0.318

GnomAD4 exome AF: 0.349 AC: 507960 AN: 1456410 Hom.: 91225 Cov.: 33 AF XY: 0.350 AC XY: 253833 AN XY: 724526

Gnomad4 AFR exome AF: 0.168

Gnomad4 AMR exome AF: 0.544

Gnomad4 ASJ exome AF: 0.373

Gnomad4 EAS exome AF: 0.445

Gnomad4 SAS exome AF: 0.407

Gnomad4 FIN exome AF: 0.303

Gnomad4 NFE exome AF: 0.340

Gnomad4 OTH exome AF: 0.344

GnomAD4 genome AF: 0.310 AC: 47109 AN: 152058 Hom.: 8006 Cov.: 33 AF XY: 0.313 AC XY: 23251 AN XY: 74316

Gnomad4 AFR AF: 0.181

Gnomad4 AMR AF: 0.446

Gnomad4 ASJ AF: 0.362

Gnomad4 EAS AF: 0.444

Gnomad4 SAS AF: 0.405

Gnomad4 FIN AF: 0.297

Gnomad4 NFE AF: 0.339

Gnomad4 OTH AF: 0.325

Alfa AF: 0.311 Hom.: 962

Bravo AF: 0.319

Asia WGS AF: 0.462 AC: 1607 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	Oct 02, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.25
DANN	Benign	0.75

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: rs12996322; hg19: chr2-233404590; COSMIC: COSV51317482; COSMIC: COSV51317482;