Genetic Variant CHRM2:c.-70T>C (chr7-136992241-T-C) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001006630.2(CHRM2):c.-70T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0453 in 152,294 control chromosomes in the GnomAD database, including 178 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.045 ( 178 hom., cov: 32)

Failed GnomAD Quality Control

Consequence

CHRM2
NM_001006630.2 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.00400

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.02).

BP6

Variant 7-136992241-T-C is Benign according to our data. Variant chr7-136992241-T-C is described in ClinVar as Benign. ClinVar VariationId is 1288157.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0671 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.-70T>C	5_prime_UTR	Exon 3 of 4	NP_001006631.1	P08172
CHRM2	NM_000739.3		c.-70T>C	5_prime_UTR	Exon 3 of 4	NP_000730.1	P08172
CHRM2	NM_001006626.3		c.-70T>C	5_prime_UTR	Exon 4 of 5	NP_001006627.1	A4D1Q0

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CHRM2	ENST00000680005.1	MANE Select	c.-70T>C	5_prime_UTR	Exon 3 of 4	ENSP00000505686.1	P08172
CHRM2	ENST00000401861.1	TSL:1	c.-70T>C	5_prime_UTR	Exon 4 of 5	ENSP00000384401.1	P08172
CHRM2	ENST00000320658.9	TSL:1	c.-46-22579T>C	intron	N/A	ENSP00000319984.5	P08172

Frequencies

GnomAD3 genomes

AF:

0.0453

AC:

6896

AN:

152176

Hom.:

179

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0362

Gnomad AMI

AF:

0.0230

Gnomad AMR

AF:

0.0296

Gnomad ASJ

AF:

0.0662

Gnomad EAS

AF:

0.000576

Gnomad SAS

AF:

0.0721

Gnomad FIN

AF:

0.0439

Gnomad MID

AF:

0.0823

Gnomad NFE

AF:

0.0551

Gnomad OTH

AF:

0.0492

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AC:

AN:

Hom.:

Cov.:

AC XY:

AN XY:

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AC:

AN:

Other (OTH)

AC:

AN:

GnomAD4 genome

AF:

0.0453

AC:

6899

AN:

152294

Hom.:

178

Cov.:

AF XY:

0.0450

AC XY:

3351

AN XY:

74468

show subpopulations

African (AFR)

AF:

0.0361

AC:

1503

AN:

41582

American (AMR)

AF:

0.0296

AC:

452

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.0662

AC:

230

AN:

3472

East Asian (EAS)

AF:

0.000578

AC:

AN:

5194

South Asian (SAS)

AF:

0.0734

AC:

354

AN:

4824

European-Finnish (FIN)

AF:

0.0439

AC:

466

AN:

10626

Middle Eastern (MID)

AF:

0.0680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0551

AC:

3746

AN:

67994

Other (OTH)

AF:

0.0492

AC:

104

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

344

689

1033

1378

1722

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

176

264

352

440

<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:

0.0464

Hom.:

118

Bravo

AF:

0.0429

Asia WGS

AF:

0.0300

AC:

105

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

5.7

(source)

DANN

Benign

0.67

PhyloP100

0.0040

Mutation Taster

=300/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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