rs10488602

Variant names:

• chr7-137005756-T-C
• rs10488602
• NM_001006630.2:c.-46-9064T>C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001006630.2(CHRM2):​c.-46-9064T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.166 in 152,074 control chromosomes in the GnomAD database, including 2,738 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 0.17 (2738 hom., cov: 32)
• Consequence: CHRM2 NM_001006630.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.31
• Publications: 4 publications found

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]

ENSG00000234352 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.424 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHRM2	NM_001006630.2	MANE Select	c.-46-9064T>C		intron	N/A	NP_001006631.1
	CHRM2	NM_000739.3		c.-46-9064T>C		intron	N/A	NP_000730.1
	CHRM2	NM_001006626.3		c.-46-9064T>C		intron	N/A	NP_001006627.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHRM2	ENST00000680005.1	MANE Select	c.-46-9064T>C		intron	N/A	ENSP00000505686.1
	CHRM2	ENST00000320658.9	TSL:1	c.-46-9064T>C		intron	N/A	ENSP00000319984.5
	CHRM2	ENST00000401861.1	TSL:1	c.-46-9064T>C		intron	N/A	ENSP00000384401.1

Frequencies

GnomAD3 genomes AF: 0.166 AC: 25205 AN: 151956 Hom.: 2732 Cov.: 32

Gnomad AFR AF: 0.0419

Gnomad AMI AF: 0.247

Gnomad AMR AF: 0.227

Gnomad ASJ AF: 0.172

Gnomad EAS AF: 0.439

Gnomad SAS AF: 0.273

Gnomad FIN AF: 0.178

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.196

Gnomad OTH AF: 0.169

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

GnomAD4 genome AF: 0.166 AC: 25211 AN: 152074 Hom.: 2738 Cov.: 32 AF XY: 0.169 AC XY: 12574 AN XY: 74322

African (AFR) AF: 0.0417 AC: 1734 AN: 41548

American (AMR) AF: 0.226 AC: 3445 AN: 15228

Ashkenazi Jewish (ASJ) AF: 0.172 AC: 595 AN: 3468

East Asian (EAS) AF: 0.440 AC: 2261 AN: 5144

South Asian (SAS) AF: 0.272 AC: 1311 AN: 4818

European-Finnish (FIN) AF: 0.178 AC: 1884 AN: 10602

Middle Eastern (MID) AF: 0.211 AC: 62 AN: 294

European-Non Finnish (NFE) AF: 0.196 AC: 13321 AN: 67956

Other (OTH) AF: 0.177 AC: 373 AN: 2106

Alfa AF: 0.189 Hom.: 5347

Bravo AF: 0.165

Asia WGS AF: 0.354 AC: 1230 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	14
DANN	Benign	0.70
PhyloP100		1.3
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10488602; hg19: chr7-136690503;