Genetic Variant CHRM2:c.-130C>T (chr7-136869413-C-T) – 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.-130C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0213 in 152,410 control chromosomes in the GnomAD database, including 179 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.021 ( 179 hom., cov: 32)

Exomes 𝑓: 0.0050 ( 0 hom. )

Consequence

CHRM2
NM_001006630.2 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.339

Publications

5 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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.57).

BP6

Variant 7-136869413-C-T is Benign according to our data. Variant chr7-136869413-C-T is described in ClinVar as Benign. ClinVar VariationId is 384814.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.18 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.-130C>T	5_prime_UTR	Exon 2 of 4	NP_001006631.1	P08172
CHRM2	NM_000739.3		c.-130C>T	5_prime_UTR	Exon 2 of 4	NP_000730.1	P08172
CHRM2	NM_001006626.3		c.-208C>T	5_prime_UTR	Exon 2 of 5	NP_001006627.1	A4D1Q0

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CHRM2	ENST00000680005.1	MANE Select	c.-130C>T	5_prime_UTR	Exon 2 of 4	ENSP00000505686.1	P08172
CHRM2	ENST00000320658.9	TSL:1	c.-52C>T	5_prime_UTR	Exon 2 of 3	ENSP00000319984.5	P08172
CHRM2	ENST00000401861.1	TSL:1	c.-208C>T	5_prime_UTR	Exon 2 of 5	ENSP00000384401.1	P08172

Frequencies

GnomAD3 genomes

AF:

0.0214

AC:

3248

AN:

152090

Hom.:

182

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00364

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0536

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.151

Gnomad SAS

AF:

0.192

Gnomad FIN

AF:

0.0211

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00454

Gnomad OTH

AF:

0.0177

GnomAD4 exome

AF:

0.00495

AC:

AN:

202

Hom.:

Cov.:

AF XY:

0.00595

AC XY:

AN XY:

168

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00556

AC:

AN:

180

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0213

AC:

3242

AN:

152208

Hom.:

179

Cov.:

AF XY:

0.0263

AC XY:

1957

AN XY:

74420

show subpopulations

African (AFR)

AF:

0.00363

AC:

151

AN:

41558

American (AMR)

AF:

0.0534

AC:

817

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00144

AC:

AN:

3468

East Asian (EAS)

AF:

0.152

AC:

782

AN:

5134

South Asian (SAS)

AF:

0.190

AC:

916

AN:

4814

European-Finnish (FIN)

AF:

0.0211

AC:

224

AN:

10614

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00454

AC:

309

AN:

68006

Other (OTH)

AF:

0.0180

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

143

286

428

571

714

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

104

156

208

260

<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:

0.00743

Hom.:

Bravo

AF:

0.0207

Asia WGS

AF:

0.157

AC:

547

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.57

CADD

Benign

7.6

(source)

DANN

Benign

0.90

PhyloP100

-0.34

PromoterAI

-0.018

Neutral

(source)

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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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