Genetic Variant CHRM2:c.-502_-501delCA (chr7-136868746-GCA-G) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_001006630.2(CHRM2):c.-502_-501delCA variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.502 in 149,326 control chromosomes in the GnomAD database, including 19,264 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.50 ( 19264 hom., cov: 0)

Exomes 𝑓: 0.18 ( 0 hom. )

Consequence

CHRM2
NM_001006630.2 5_prime_UTR

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.214

Publications

3 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP6

Variant 7-136868746-GCA-G is Benign according to our data. Variant chr7-136868746-GCA-G is described in ClinVar as Benign. ClinVar VariationId is 1290257.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.774 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.-502_-501delCA	5_prime_UTR	Exon 1 of 4	NP_001006631.1	P08172
CHRM2	NM_001006627.3		c.-424_-423delCA	5_prime_UTR	Exon 1 of 3	NP_001006628.1	A4D1Q0
CHRM2	NM_001378972.1		c.-614_-613delCA	5_prime_UTR	Exon 1 of 5	NP_001365901.1	P08172

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CHRM2	ENST00000680005.1	MANE Select	c.-502_-501delCA	5_prime_UTR	Exon 1 of 4	ENSP00000505686.1	P08172
CHRM2	ENST00000445907.6	TSL:1	c.-424_-423delCA	5_prime_UTR	Exon 1 of 3	ENSP00000399745.2	P08172
ENSG00000234352	ENST00000439694.6	TSL:1	n.656-82857_656-82856delTG	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.503

AC:

74967

AN:

149028

Hom.:

19260

Cov.:

show subpopulations

Gnomad AFR

AF:

0.382

Gnomad AMI

AF:

0.355

Gnomad AMR

AF:

0.581

Gnomad ASJ

AF:

0.525

Gnomad EAS

AF:

0.796

Gnomad SAS

AF:

0.497

Gnomad FIN

AF:

0.645

Gnomad MID

AF:

0.500

Gnomad NFE

AF:

0.517

Gnomad OTH

AF:

0.525

GnomAD4 exome

AF:

0.175

AC:

AN:

194

Hom.:

AF XY:

0.179

AC XY:

AN XY:

162

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.375

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.174

AC:

AN:

172

Other (OTH)

AF:

0.125

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.521

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.503

AC:

74996

AN:

149132

Hom.:

19264

Cov.:

AF XY:

0.513

AC XY:

37306

AN XY:

72670

show subpopulations

African (AFR)

AF:

0.381

AC:

15546

AN:

40754

American (AMR)

AF:

0.582

AC:

8731

AN:

15004

Ashkenazi Jewish (ASJ)

AF:

0.525

AC:

1801

AN:

3430

East Asian (EAS)

AF:

0.795

AC:

3914

AN:

4922

South Asian (SAS)

AF:

0.497

AC:

2320

AN:

4672

European-Finnish (FIN)

AF:

0.645

AC:

6490

AN:

10064

Middle Eastern (MID)

AF:

0.489

AC:

137

AN:

280

European-Non Finnish (NFE)

AF:

0.517

AC:

34641

AN:

67028

Other (OTH)

AF:

0.529

AC:

1094

AN:

2070

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

1693

3386

5078

6771

8464

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

676

1352

2028

2704

3380

<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:

0.339

Hom.:

771

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

PhyloP100

-0.21

Mutation Taster

=300/0

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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7-136868746-GCACACACACACACACA-GCACACACACACACA

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