chr2-232542288-T-G

Position:

• chr2-232542288-T-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_005199.5(CHRNG):​c.507-135T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.814 in 692,560 control chromosomes in the GnomAD database, including 230,215 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.81 (49908 hom., cov: 31)
  • Exomes 𝑓: 0.82 (180307 hom.)
• Consequence: CHRNG NM_005199.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.486

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 2-232542288-T-G is Benign according to our data. Variant chr2-232542288-T-G is described in ClinVar as [Benign]. Clinvar id is 1246168.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.85 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHRNG	NM_005199.5	c.507-135T>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.507-135T>G		intron_variant			NM_005199.5	ENSP00000498757	P1
CHRNG	ENST00000389492.3	c.351-135T>G		intron_variant		1		ENSP00000374143

Frequencies

GnomAD3 genomes AF: 0.809 AC: 122995 AN: 151984 Hom.: 49868 Cov.: 31

Gnomad AFR AF: 0.803

Gnomad AMI AF: 0.808

Gnomad AMR AF: 0.818

Gnomad ASJ AF: 0.887

Gnomad EAS AF: 0.871

Gnomad SAS AF: 0.841

Gnomad FIN AF: 0.796

Gnomad MID AF: 0.848

Gnomad NFE AF: 0.802

Gnomad OTH AF: 0.803

GnomAD4 exome AF: 0.816 AC: 440938 AN: 540458 Hom.: 180307 AF XY: 0.817 AC XY: 237408 AN XY: 290528

Gnomad4 AFR exome AF: 0.800

Gnomad4 AMR exome AF: 0.846

Gnomad4 ASJ exome AF: 0.882

Gnomad4 EAS exome AF: 0.856

Gnomad4 SAS exome AF: 0.832

Gnomad4 FIN exome AF: 0.792

Gnomad4 NFE exome AF: 0.805

Gnomad4 OTH exome AF: 0.818

GnomAD4 genome AF: 0.809 AC: 123091 AN: 152102 Hom.: 49908 Cov.: 31 AF XY: 0.811 AC XY: 60259 AN XY: 74342

Gnomad4 AFR AF: 0.803

Gnomad4 AMR AF: 0.818

Gnomad4 ASJ AF: 0.887

Gnomad4 EAS AF: 0.872

Gnomad4 SAS AF: 0.840

Gnomad4 FIN AF: 0.796

Gnomad4 NFE AF: 0.802

Gnomad4 OTH AF: 0.805

Alfa AF: 0.805 Hom.: 54909

Bravo AF: 0.812

Asia WGS AF: 0.861 AC: 2991 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

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	-0.83
CADD	Benign	2.5
DANN	Benign	0.55

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: rs1881492; hg19: chr2-233406998;