rs12996322

Variant names:

• chr2-232539880-G-A
• rs12996322
• NM_005199.5:c.55+78G>A

Your query was ambiguous. Multiple possible variants found:

• chr2-232539880-G-A
• chr2-232539880-G-C
• chr2-232539880-G-T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_005199.5(CHRNG):​c.55+78G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CHRNG NM_005199.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.59
• Publications: 8 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHRNG	NM_005199.5	c.55+78G>A		intron_variant	Intron 1 of 11	ENST00000651502.1	NP_005190.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHRNG	ENST00000651502.1	c.55+78G>A		intron_variant	Intron 1 of 11		NM_005199.5	ENSP00000498757.1
CHRNG	ENST00000389492.3	c.55+78G>A		intron_variant	Intron 1 of 10	1		ENSP00000374143.3
CHRNG	ENST00000485094.1	n.76+78G>A		intron_variant	Intron 1 of 4	1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 151984 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1456908 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 724762

African (AFR) AF: 0.00 AC: 0 AN: 33352

American (AMR) AF: 0.00 AC: 0 AN: 44654

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26084

East Asian (EAS) AF: 0.00 AC: 0 AN: 39662

South Asian (SAS) AF: 0.00 AC: 0 AN: 86146

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53122

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4840

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1108898

Other (OTH) AF: 0.00 AC: 0 AN: 60150

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 151984 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74214

African (AFR) AF: 0.00 AC: 0 AN: 41398

American (AMR) AF: 0.00 AC: 0 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10588

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67952

Other (OTH) AF: 0.00 AC: 0 AN: 2088

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.31
DANN	Benign	0.93
PhyloP100		-1.6
PromoterAI		-0.016	Neutral

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: rs12996322; hg19: chr2-233404590;