dbSNP rs28529003: CHRM2:c.-124-41383T>A (chr7-136950804-T-A) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001006630.2(CHRM2):c.-124-41383T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.649 in 150,922 control chromosomes in the GnomAD database, including 32,133 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.65 ( 32133 hom., cov: 30)

Consequence

CHRM2
NM_001006630.2 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.299

Publications

0 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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.95).

BP6

Variant 7-136950804-T-A is Benign according to our data. Variant chr7-136950804-T-A is described in ClinVar as Benign. ClinVar VariationId is 1224957.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.71 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.-124-41383T>A	intron	N/A	NP_001006631.1	P08172
CHRM2	NM_000739.3		c.-124-41383T>A	intron	N/A	NP_000730.1	P08172
CHRM2	NM_001006626.3		c.-202-199T>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.-124-41383T>A	intron	N/A	ENSP00000505686.1	P08172
CHRM2	ENST00000320658.9	TSL:1	c.-46-64016T>A	intron	N/A	ENSP00000319984.5	P08172
CHRM2	ENST00000401861.1	TSL:1	c.-202-199T>A	intron	N/A	ENSP00000384401.1	P08172

Frequencies

GnomAD3 genomes

AF:

0.649

AC:

97830

AN:

150810

Hom.:

32102

Cov.:

show subpopulations

Gnomad AFR

AF:

0.717

Gnomad AMI

AF:

0.609

Gnomad AMR

AF:

0.520

Gnomad ASJ

AF:

0.661

Gnomad EAS

AF:

0.452

Gnomad SAS

AF:

0.480

Gnomad FIN

AF:

0.671

Gnomad MID

AF:

0.593

Gnomad NFE

AF:

0.660

Gnomad OTH

AF:

0.639

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

GnomAD4 genome

AF:

0.649

AC:

97905

AN:

150922

Hom.:

32133

Cov.:

AF XY:

0.644

AC XY:

47477

AN XY:

73744

show subpopulations

African (AFR)

AF:

0.717

AC:

29281

AN:

40832

American (AMR)

AF:

0.519

AC:

7876

AN:

15168

Ashkenazi Jewish (ASJ)

AF:

0.661

AC:

2293

AN:

3468

East Asian (EAS)

AF:

0.451

AC:

2276

AN:

5052

South Asian (SAS)

AF:

0.481

AC:

2300

AN:

4782

European-Finnish (FIN)

AF:

0.671

AC:

7034

AN:

10482

Middle Eastern (MID)

AF:

0.600

AC:

174

AN:

290

European-Non Finnish (NFE)

AF:

0.660

AC:

44769

AN:

67840

Other (OTH)

AF:

0.642

AC:

1349

AN:

2100

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

1687

3375

5062

6750

8437

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

786

1572

2358

3144

3930

<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:

0.657

Hom.:

3889

Bravo

AF:

0.638

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

2.4

(source)

DANN

Benign

0.24

PhyloP100

0.30

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