rs6761667

Variant names:

• chr2-232542701-T-A
• rs6761667
• NM_005199.5:c.604+181T>A

Your query was ambiguous. Multiple possible variants found:

• chr2-232542701-T-A
• chr2-232542701-T-C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 publications found

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]

CHRNG Gene-Disease associations (from GenCC):

• autosomal recessive multiple pterygium syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, G2P, Orphanet
• CHRNG-associated hypo-akinesia disorder of prenatal onset

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• lethal multiple pterygium syndrome

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), Orphanet
• transient neonatal myasthenia gravis

  Inheritance: AR Classification: STRONG Submitted by: Genomics England PanelApp

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
CHRNG	NM_005199.5	c.604+181T>A		intron_variant	Intron 6 of 11	ENST00000651502.1	NP_005190.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHRNG	ENST00000651502.1	c.604+181T>A		intron_variant	Intron 6 of 11		NM_005199.5	ENSP00000498757.1
CHRNG	ENST00000389492.3	c.448+181T>A		intron_variant	Intron 5 of 10	1		ENSP00000374143.3

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

African (AFR) AF: 0.359 AC: 14880 AN: 41466

American (AMR) AF: 0.567 AC: 8653 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.583 AC: 2023 AN: 3470

East Asian (EAS) AF: 0.530 AC: 2727 AN: 5144

South Asian (SAS) AF: 0.595 AC: 2867 AN: 4818

European-Finnish (FIN) AF: 0.430 AC: 4552 AN: 10578

Middle Eastern (MID) AF: 0.592 AC: 174 AN: 294

European-Non Finnish (NFE) AF: 0.462 AC: 31403 AN: 67970

Other (OTH) AF: 0.483 AC: 1019 AN: 2110

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

Nov 10, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.24
DANN	Benign	0.71
PhyloP100		-0.24
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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