Genetic Variant CHRM2:c.-47+359T>C (chr7-136992623-T-C) – 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.-47+359T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.647 in 152,042 control chromosomes in the GnomAD database, including 32,974 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 0.65 ( 32974 hom., cov: 33)

Consequence

CHRM2
NM_001006630.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.91

Publications

1 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=-1.0).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.728 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.-47+359T>C	intron	N/A	NP_001006631.1	P08172
CHRM2	NM_000739.3		c.-47+359T>C	intron	N/A	NP_000730.1	P08172
CHRM2	NM_001006626.3		c.-47+359T>C	intron	N/A	NP_001006627.1	A4D1Q0

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CHRM2	ENST00000680005.1	MANE Select	c.-47+359T>C	intron	N/A	ENSP00000505686.1	P08172
CHRM2	ENST00000320658.9	TSL:1	c.-46-22197T>C	intron	N/A	ENSP00000319984.5	P08172
CHRM2	ENST00000401861.1	TSL:1	c.-47+359T>C	intron	N/A	ENSP00000384401.1	P08172

Frequencies

GnomAD3 genomes

AF:

0.647

AC:

98367

AN:

151924

Hom.:

32953

Cov.:

show subpopulations

Gnomad AFR

AF:

0.518

Gnomad AMI

AF:

0.626

Gnomad AMR

AF:

0.559

Gnomad ASJ

AF:

0.781

Gnomad EAS

AF:

0.385

Gnomad SAS

AF:

0.605

Gnomad FIN

AF:

0.825

Gnomad MID

AF:

0.734

Gnomad NFE

AF:

0.734

Gnomad OTH

AF:

0.672

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

GnomAD4 genome

AF:

0.647

AC:

98416

AN:

152042

Hom.:

32974

Cov.:

AF XY:

0.652

AC XY:

48424

AN XY:

74316

show subpopulations

African (AFR)

AF:

0.518

AC:

21491

AN:

41492

American (AMR)

AF:

0.558

AC:

8513

AN:

15244

Ashkenazi Jewish (ASJ)

AF:

0.781

AC:

2708

AN:

3466

East Asian (EAS)

AF:

0.385

AC:

1991

AN:

5166

South Asian (SAS)

AF:

0.606

AC:

2925

AN:

4824

European-Finnish (FIN)

AF:

0.825

AC:

8735

AN:

10586

Middle Eastern (MID)

AF:

0.724

AC:

213

AN:

294

European-Non Finnish (NFE)

AF:

0.734

AC:

49847

AN:

67952

Other (OTH)

AF:

0.675

AC:

1425

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1700

3400

5101

6801

8501

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

782

1564

2346

3128

3910

<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:

0.596

Hom.:

2014

Bravo

AF:

0.618

Asia WGS

AF:

0.509

AC:

1772

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.030

(source)

DANN

Benign

0.24

PhyloP100

-1.9

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