dbSNP rs7810473: CHRM2:c.-125+42292A>G (chr7-136911710-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001006630.2(CHRM2):c.-125+42292A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.399 in 151,852 control chromosomes in the GnomAD database, including 12,758 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 0.40 ( 12758 hom., cov: 32)

Consequence

CHRM2
NM_001006630.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.38

Publications

6 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]

CHRM2 links:

ENSG00000234352 (HGNC:):

ENSG00000234352 links:

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new If you want to explore the variant's impact on the transcript NM_001006630.2, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

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=-0.96).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.44 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001006630.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CHRM2	NM_001006630.2	MANE Select	c.-125+42292A>G	intron	N/A	NP_001006631.1	P08172
CHRM2	NM_000739.3		c.-125+42292A>G	intron	N/A	NP_000730.1	P08172
CHRM2	NM_001006626.3		c.-202-39293A>G	intron	N/A	NP_001006627.1	A4D1Q0

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CHRM2	ENST00000680005.1	MANE Select	c.-125+42292A>G	intron	N/A	ENSP00000505686.1	P08172
CHRM2	ENST00000320658.9	TSL:1	c.-47+42292A>G	intron	N/A	ENSP00000319984.5	P08172
CHRM2	ENST00000401861.1	TSL:1	c.-202-39293A>G	intron	N/A	ENSP00000384401.1	P08172

Frequencies

GnomAD3 genomes

AF:

0.399

AC:

60488

AN:

151732

Hom.:

12747

Cov.:

show subpopulations

Gnomad AFR

AF:

0.445

Gnomad AMI

AF:

0.434

Gnomad AMR

AF:

0.320

Gnomad ASJ

AF:

0.444

Gnomad EAS

AF:

0.0412

Gnomad SAS

AF:

0.172

Gnomad FIN

AF:

0.420

Gnomad MID

AF:

0.415

Gnomad NFE

AF:

0.425

Gnomad OTH

AF:

0.400

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.399

AC:

60526

AN:

151852

Hom.:

12758

Cov.:

AF XY:

0.392

AC XY:

29070

AN XY:

74186

show subpopulations

African (AFR)

AF:

0.445

AC:

18439

AN:

41442

American (AMR)

AF:

0.320

AC:

4876

AN:

15244

Ashkenazi Jewish (ASJ)

AF:

0.444

AC:

1539

AN:

3466

East Asian (EAS)

AF:

0.0407

AC:

209

AN:

5138

South Asian (SAS)

AF:

0.172

AC:

829

AN:

4826

European-Finnish (FIN)

AF:

0.420

AC:

4433

AN:

10564

Middle Eastern (MID)

AF:

0.415

AC:

122

AN:

294

European-Non Finnish (NFE)

AF:

0.425

AC:

28848

AN:

67856

Other (OTH)

AF:

0.396

AC:

836

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1818

3635

5453

7270

9088

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

552

1104

1656

2208

2760

<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:

0.404

Hom.:

21090

Bravo

AF:

0.393

Asia WGS

AF:

0.147

AC:

512

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.96

CADD

Benign

0.13

(source)

DANN

Benign

0.20

PhyloP100

-1.4

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over