chr2-232542701-T-A

Position:

• chr2-232542701-T-A

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.604+181T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.452 in 152,032 control chromosomes in the GnomAD database, including 16,044 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.45 (16044 hom., cov: 33)
• Consequence: CHRNG NM_005199.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.239

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=-0.89).
• BP6: Variant 2-232542701-T-A is Benign according to our data. Variant chr2-232542701-T-A is described in ClinVar as [Benign]. Clinvar id is 1260524.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.577 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHRNG	NM_005199.5	c.604+181T>A		intron_variant		ENST00000651502.1	NP_005190.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHRNG	ENST00000651502.1	c.604+181T>A		intron_variant			NM_005199.5	ENSP00000498757	P1
CHRNG	ENST00000389492.3	c.448+181T>A		intron_variant		1		ENSP00000374143

Frequencies

GnomAD3 genomes AF: 0.452 AC: 68680 AN: 151914 Hom.: 16023 Cov.: 33

Gnomad AFR AF: 0.359

Gnomad AMI AF: 0.471

Gnomad AMR AF: 0.566

Gnomad ASJ AF: 0.583

Gnomad EAS AF: 0.530

Gnomad SAS AF: 0.596

Gnomad FIN AF: 0.430

Gnomad MID AF: 0.589

Gnomad NFE AF: 0.462

Gnomad OTH AF: 0.479

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.452 AC: 68728 AN: 152032 Hom.: 16044 Cov.: 33 AF XY: 0.457 AC XY: 33942 AN XY: 74296

Gnomad4 AFR AF: 0.359

Gnomad4 AMR AF: 0.567

Gnomad4 ASJ AF: 0.583

Gnomad4 EAS AF: 0.530

Gnomad4 SAS AF: 0.595

Gnomad4 FIN AF: 0.430

Gnomad4 NFE AF: 0.462

Gnomad4 OTH AF: 0.483

Alfa AF: 0.445 Hom.: 2056

Bravo AF: 0.459

Asia WGS AF: 0.594 AC: 2066 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	-0.89
CADD	Benign	0.24
DANN	Benign	0.71

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: rs6761667; hg19: chr2-233407411; COSMIC: COSV67315374; COSMIC: COSV67315374;