2-232539880-G-C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_005199.5(CHRNG):​c.55+78G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.345 in 1,608,468 control chromosomes in the GnomAD database, including 99,231 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.31 ( 8006 hom., cov: 33)
Exomes 𝑓: 0.35 ( 91225 hom. )

Consequence

CHRNG
NM_005199.5 intron

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.59

Publications

8 publications found
Variant links:
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

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.91).
BP6
Variant 2-232539880-G-C is Benign according to our data. Variant chr2-232539880-G-C is described in ClinVar as [Benign]. Clinvar id is 1290181.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.437 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CHRNGNM_005199.5 linkc.55+78G>C intron_variant Intron 1 of 11 ENST00000651502.1 NP_005190.4 P07510-1A0A6F7YAP6

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CHRNGENST00000651502.1 linkc.55+78G>C intron_variant Intron 1 of 11 NM_005199.5 ENSP00000498757.1 P07510-1
CHRNGENST00000389492.3 linkc.55+78G>C intron_variant Intron 1 of 10 1 ENSP00000374143.3 P07510-2
CHRNGENST00000485094.1 linkn.76+78G>C intron_variant Intron 1 of 4 1

Frequencies

GnomAD3 genomes
AF:
0.310
AC:
47073
AN:
151940
Hom.:
7988
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.181
Gnomad AMI
AF:
0.400
Gnomad AMR
AF:
0.445
Gnomad ASJ
AF:
0.362
Gnomad EAS
AF:
0.444
Gnomad SAS
AF:
0.405
Gnomad FIN
AF:
0.297
Gnomad MID
AF:
0.329
Gnomad NFE
AF:
0.339
Gnomad OTH
AF:
0.318
GnomAD4 exome
AF:
0.349
AC:
507960
AN:
1456410
Hom.:
91225
Cov.:
33
AF XY:
0.350
AC XY:
253833
AN XY:
724526
show subpopulations
African (AFR)
AF:
0.168
AC:
5589
AN:
33350
American (AMR)
AF:
0.544
AC:
24307
AN:
44650
Ashkenazi Jewish (ASJ)
AF:
0.373
AC:
9718
AN:
26078
East Asian (EAS)
AF:
0.445
AC:
17630
AN:
39662
South Asian (SAS)
AF:
0.407
AC:
35073
AN:
86128
European-Finnish (FIN)
AF:
0.303
AC:
16100
AN:
53106
Middle Eastern (MID)
AF:
0.327
AC:
1580
AN:
4834
European-Non Finnish (NFE)
AF:
0.340
AC:
377264
AN:
1108470
Other (OTH)
AF:
0.344
AC:
20699
AN:
60132
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.497
Heterozygous variant carriers
0
18395
36789
55184
73578
91973
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
12240
24480
36720
48960
61200
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.310
AC:
47109
AN:
152058
Hom.:
8006
Cov.:
33
AF XY:
0.313
AC XY:
23251
AN XY:
74316
show subpopulations
African (AFR)
AF:
0.181
AC:
7505
AN:
41514
American (AMR)
AF:
0.446
AC:
6809
AN:
15280
Ashkenazi Jewish (ASJ)
AF:
0.362
AC:
1257
AN:
3468
East Asian (EAS)
AF:
0.444
AC:
2289
AN:
5158
South Asian (SAS)
AF:
0.405
AC:
1950
AN:
4812
European-Finnish (FIN)
AF:
0.297
AC:
3145
AN:
10584
Middle Eastern (MID)
AF:
0.344
AC:
101
AN:
294
European-Non Finnish (NFE)
AF:
0.339
AC:
23003
AN:
67926
Other (OTH)
AF:
0.325
AC:
685
AN:
2110
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.503
Heterozygous variant carriers
0
1651
3303
4954
6606
8257
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
476
952
1428
1904
2380
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.311
Hom.:
962
Bravo
AF:
0.319
Asia WGS
AF:
0.462
AC:
1607
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Oct 02, 2019
GeneDx
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

-
Breakthrough Genomics, Breakthrough Genomics
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.91
CADD
Benign
0.25
DANN
Benign
0.75
PhyloP100
-1.6
PromoterAI
-0.021
Neutral
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

Publications

Other links and lift over

dbSNP: rs12996322; hg19: chr2-233404590; COSMIC: COSV51317482; COSMIC: COSV51317482; API