rs11674608

Variant names:

• chr2-232539584-C-G
• rs11674608
• NM_005199.5:c.-164C>G

Your query was ambiguous. Multiple possible variants found:

• chr2-232539584-C-G
• chr2-232539584-C-A
• chr2-232539584-C-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_005199.5(CHRNG):​c.-164C>G variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.385 in 714,464 control chromosomes in the GnomAD database, including 55,866 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.36 (10316 hom., cov: 33)
  • Exomes 𝑓: 0.39 (45550 hom.)
• Consequence: CHRNG NM_005199.5 upstream_gene
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.833
• 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: G2P, Ambry Genetics, 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: 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BP6: Variant 2-232539584-C-G is Benign according to our data. Variant chr2-232539584-C-G is described in ClinVar as Benign. ClinVar VariationId is 1293032.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.539 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005199.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHRNG	NM_005199.5	MANE Select	c.-164C>G		upstream_gene	N/A	NP_005190.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHRNG	ENST00000651502.1	MANE Select	c.-164C>G		upstream_gene	N/A	ENSP00000498757.1	P07510-1
	CHRNG	ENST00000389492.3	TSL:1	c.-164C>G		upstream_gene	N/A	ENSP00000374143.3	P07510-2
	CHRNG	ENST00000485094.1	TSL:1	n.-143C>G		upstream_gene	N/A

Frequencies

GnomAD3 genomes AF: 0.358 AC: 54379 AN: 152052 Hom.: 10292 Cov.: 33

Gnomad AFR AF: 0.280

Gnomad AMI AF: 0.404

Gnomad AMR AF: 0.497

Gnomad ASJ AF: 0.362

Gnomad EAS AF: 0.557

Gnomad SAS AF: 0.430

Gnomad FIN AF: 0.330

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.356

Gnomad OTH AF: 0.366

GnomAD4 exome AF: 0.392 AC: 220486 AN: 562296 Hom.: 45550 AF XY: 0.392 AC XY: 117815 AN XY: 300318

African (AFR) AF: 0.271 AC: 4508 AN: 16630

American (AMR) AF: 0.607 AC: 22745 AN: 37442

Ashkenazi Jewish (ASJ) AF: 0.375 AC: 6345 AN: 16940

East Asian (EAS) AF: 0.565 AC: 19837 AN: 35136

South Asian (SAS) AF: 0.430 AC: 25625 AN: 59588

European-Finnish (FIN) AF: 0.332 AC: 11728 AN: 35336

Middle Eastern (MID) AF: 0.337 AC: 877 AN: 2600

European-Non Finnish (NFE) AF: 0.357 AC: 117239 AN: 328218

Other (OTH) AF: 0.381 AC: 11582 AN: 30406

GnomAD4 genome AF: 0.358 AC: 54440 AN: 152168 Hom.: 10316 Cov.: 33 AF XY: 0.360 AC XY: 26799 AN XY: 74374

African (AFR) AF: 0.280 AC: 11625 AN: 41522

American (AMR) AF: 0.498 AC: 7617 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.362 AC: 1258 AN: 3472

East Asian (EAS) AF: 0.556 AC: 2871 AN: 5160

South Asian (SAS) AF: 0.431 AC: 2076 AN: 4822

European-Finnish (FIN) AF: 0.330 AC: 3501 AN: 10600

Middle Eastern (MID) AF: 0.357 AC: 105 AN: 294

European-Non Finnish (NFE) AF: 0.357 AC: 24235 AN: 67978

Other (OTH) AF: 0.372 AC: 784 AN: 2110

Alfa AF: 0.212 Hom.: 475

Bravo AF: 0.371

Asia WGS AF: 0.525 AC: 1824 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	2.6
DANN	Benign	0.78
PhyloP100		-0.83
PromoterAI		0.026	Neutral
Mutation Taster		=100/0	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs11674608; hg19: chr2-233404294; COSMIC: COSV51328207;