dbSNP rs324650: CHRM2:c.-46-5906T>A (chr7-137008914-T-A) – 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.-46-5906T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.538 in 151,828 control chromosomes in the GnomAD database, including 23,372 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 0.54 ( 23372 hom., cov: 32)

Consequence

CHRM2
NM_001006630.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0300

Publications

38 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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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 = 0.666 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.-46-5906T>A	intron	N/A	NP_001006631.1	P08172
CHRM2	NM_000739.3		c.-46-5906T>A	intron	N/A	NP_000730.1	P08172
CHRM2	NM_001006626.3		c.-46-5906T>A	intron	N/A	NP_001006627.1	A4D1Q0

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CHRM2	ENST00000680005.1	MANE Select	c.-46-5906T>A	intron	N/A	ENSP00000505686.1	P08172
CHRM2	ENST00000320658.9	TSL:1	c.-46-5906T>A	intron	N/A	ENSP00000319984.5	P08172
CHRM2	ENST00000401861.1	TSL:1	c.-46-5906T>A	intron	N/A	ENSP00000384401.1	P08172

Frequencies

GnomAD3 genomes

AF:

0.538

AC:

81663

AN:

151710

Hom.:

23333

Cov.:

show subpopulations

Gnomad AFR

AF:

0.672

Gnomad AMI

AF:

0.545

Gnomad AMR

AF:

0.411

Gnomad ASJ

AF:

0.568

Gnomad EAS

AF:

0.0818

Gnomad SAS

AF:

0.250

Gnomad FIN

AF:

0.577

Gnomad MID

AF:

0.595

Gnomad NFE

AF:

0.532

Gnomad OTH

AF:

0.544

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

GnomAD4 genome

AF:

0.538

AC:

81744

AN:

151828

Hom.:

23372

Cov.:

AF XY:

0.532

AC XY:

39434

AN XY:

74178

show subpopulations

African (AFR)

AF:

0.673

AC:

27876

AN:

41424

American (AMR)

AF:

0.410

AC:

6241

AN:

15224

Ashkenazi Jewish (ASJ)

AF:

0.568

AC:

1972

AN:

3472

East Asian (EAS)

AF:

0.0816

AC:

420

AN:

5148

South Asian (SAS)

AF:

0.251

AC:

1209

AN:

4824

European-Finnish (FIN)

AF:

0.577

AC:

6089

AN:

10552

Middle Eastern (MID)

AF:

0.588

AC:

173

AN:

294

European-Non Finnish (NFE)

AF:

0.532

AC:

36134

AN:

67872

Other (OTH)

AF:

0.538

AC:

1135

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1818

3636

5453

7271

9089

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

678

1356

2034

2712

3390

<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:

0.548

Hom.:

2882

Bravo

AF:

0.533

Asia WGS

AF:

0.224

AC:

779

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

0.97

(source)

DANN

Benign

0.72

PhyloP100

0.030

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

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