7-136986811-G-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001006630.2(CHRM2):​c.-124-5376G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.607 in 151,988 control chromosomes in the GnomAD database, including 29,079 homozygotes. 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 0.61 ( 29079 hom., cov: 32)

Consequence

CHRM2
NM_001006630.2 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.486

Publications

3 publications found
Variant links:
Genes affected
CHRM2 (HGNC:1951): (cholinergic receptor muscarinic 2) The muscarinic cholinergic receptors belong to a larger family of G protein-coupled receptors. The functional diversity of these receptors is defined by the binding of acetylcholine to these receptors and includes cellular responses such as adenylate cyclase inhibition, phosphoinositide degeneration, and potassium channel mediation. Muscarinic receptors influence many effects of acetylcholine in the central and peripheral nervous system. The muscarinic cholinergic receptor 2 is involved in mediation of bradycardia and a decrease in cardiac contractility. Multiple alternatively spliced transcript variants have been described for this gene. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.99).
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.681 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CHRM2NM_001006630.2 linkc.-124-5376G>C intron_variant Intron 2 of 3 ENST00000680005.1 NP_001006631.1 P08172A4D1Q0Q6SL56Q86SJ1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CHRM2ENST00000680005.1 linkc.-124-5376G>C intron_variant Intron 2 of 3 NM_001006630.2 ENSP00000505686.1 P08172

Frequencies

GnomAD3 genomes
AF:
0.607
AC:
92232
AN:
151868
Hom.:
29059
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.487
Gnomad AMI
AF:
0.602
Gnomad AMR
AF:
0.530
Gnomad ASJ
AF:
0.723
Gnomad EAS
AF:
0.360
Gnomad SAS
AF:
0.551
Gnomad FIN
AF:
0.782
Gnomad MID
AF:
0.668
Gnomad NFE
AF:
0.686
Gnomad OTH
AF:
0.626
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.607
AC:
92278
AN:
151988
Hom.:
29079
Cov.:
32
AF XY:
0.611
AC XY:
45410
AN XY:
74284
show subpopulations
African (AFR)
AF:
0.487
AC:
20186
AN:
41436
American (AMR)
AF:
0.529
AC:
8070
AN:
15256
Ashkenazi Jewish (ASJ)
AF:
0.723
AC:
2510
AN:
3472
East Asian (EAS)
AF:
0.361
AC:
1862
AN:
5158
South Asian (SAS)
AF:
0.551
AC:
2656
AN:
4816
European-Finnish (FIN)
AF:
0.782
AC:
8262
AN:
10562
Middle Eastern (MID)
AF:
0.673
AC:
198
AN:
294
European-Non Finnish (NFE)
AF:
0.686
AC:
46657
AN:
67970
Other (OTH)
AF:
0.629
AC:
1328
AN:
2112
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.502
Heterozygous variant carriers
0
1750
3501
5251
7002
8752
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
758
1516
2274
3032
3790
<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:
0.544
Hom.:
1691
Bravo
AF:
0.580
Asia WGS
AF:
0.479
AC:
1668
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.99
CADD
Benign
0.70
DANN
Benign
0.40
PhyloP100
-0.49
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: rs7799047; hg19: chr7-136671558; API