Genetic Variant NM_001006630.2:c.*2363T>C (chr7-137018629-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.*2363T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.591 in 151,628 control chromosomes in the GnomAD database, including 27,837 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 0.59 ( 27835 hom., cov: 31)

Exomes 𝑓: 0.56 ( 2 hom. )

Consequence

CHRM2
NM_001006630.2 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.121

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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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=-0.89).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.697 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.*2363T>C	3_prime_UTR	Exon 4 of 4	NP_001006631.1	P08172
CHRM2	NM_000739.3		c.*2363T>C	3_prime_UTR	Exon 4 of 4	NP_000730.1	P08172
CHRM2	NM_001006626.3		c.*2363T>C	3_prime_UTR	Exon 5 of 5	NP_001006627.1	A4D1Q0

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CHRM2	ENST00000680005.1	MANE Select	c.*2363T>C	3_prime_UTR	Exon 4 of 4	ENSP00000505686.1	P08172
CHRM2	ENST00000445907.6	TSL:1	c.*2363T>C	3_prime_UTR	Exon 3 of 3	ENSP00000399745.2	P08172
ENSG00000234352	ENST00000439694.6	TSL:1	n.655+13276A>G	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.591

AC:

89545

AN:

151490

Hom.:

27806

Cov.:

show subpopulations

Gnomad AFR

AF:

0.704

Gnomad AMI

AF:

0.590

Gnomad AMR

AF:

0.463

Gnomad ASJ

AF:

0.630

Gnomad EAS

AF:

0.102

Gnomad SAS

AF:

0.283

Gnomad FIN

AF:

0.641

Gnomad MID

AF:

0.640

Gnomad NFE

AF:

0.600

Gnomad OTH

AF:

0.597

GnomAD4 exome

AF:

0.556

AC:

AN:

Hom.:

Cov.:

AF XY:

0.625

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.500

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.643

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.542

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.591

AC:

89611

AN:

151610

Hom.:

27835

Cov.:

AF XY:

0.584

AC XY:

43214

AN XY:

74058

show subpopulations

African (AFR)

AF:

0.704

AC:

29125

AN:

41388

American (AMR)

AF:

0.462

AC:

7018

AN:

15180

Ashkenazi Jewish (ASJ)

AF:

0.630

AC:

2184

AN:

3466

East Asian (EAS)

AF:

0.102

AC:

523

AN:

5112

South Asian (SAS)

AF:

0.283

AC:

1365

AN:

4818

European-Finnish (FIN)

AF:

0.641

AC:

6749

AN:

10530

Middle Eastern (MID)

AF:

0.639

AC:

188

AN:

294

European-Non Finnish (NFE)

AF:

0.600

AC:

40681

AN:

67810

Other (OTH)

AF:

0.590

AC:

1241

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1751

3501

5252

7002

8753

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

722

1444

2166

2888

3610

<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:

0.594

Hom.:

73541

Bravo

AF:

0.584

Asia WGS

AF:

0.255

AC:

890

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

3.6

(source)

DANN

Benign

0.52

PhyloP100

0.12

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