rs10488597

Variant names:

• chr7-136876185-T-C
• rs10488597
• NM_001006630.2:c.-125+6767T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001006630.2(CHRM2):​c.-125+6767T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.162 in 152,142 control chromosomes in the GnomAD database, including 2,371 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 0.16 (2371 hom., cov: 32)
• Consequence: CHRM2 NM_001006630.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.08
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.222 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHRM2	NM_001006630.2	c.-125+6767T>C		intron_variant	Intron 2 of 3	ENST00000680005.1	NP_001006631.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHRM2	ENST00000680005.1	c.-125+6767T>C		intron_variant	Intron 2 of 3		NM_001006630.2	ENSP00000505686.1

Frequencies

GnomAD3 genomes AF: 0.162 AC: 24662 AN: 152024 Hom.: 2373 Cov.: 32

Gnomad AFR AF: 0.0766

Gnomad AMI AF: 0.185

Gnomad AMR AF: 0.151

Gnomad ASJ AF: 0.199

Gnomad EAS AF: 0.0100

Gnomad SAS AF: 0.103

Gnomad FIN AF: 0.199

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.225

Gnomad OTH AF: 0.162

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

GnomAD4 genome AF: 0.162 AC: 24647 AN: 152142 Hom.: 2371 Cov.: 32 AF XY: 0.157 AC XY: 11669 AN XY: 74370

African (AFR) AF: 0.0764 AC: 3174 AN: 41532

American (AMR) AF: 0.150 AC: 2294 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.199 AC: 690 AN: 3472

East Asian (EAS) AF: 0.00985 AC: 51 AN: 5176

South Asian (SAS) AF: 0.102 AC: 490 AN: 4824

European-Finnish (FIN) AF: 0.199 AC: 2110 AN: 10590

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.225 AC: 15293 AN: 67966

Other (OTH) AF: 0.160 AC: 338 AN: 2112

Alfa AF: 0.204 Hom.: 1675

Bravo AF: 0.154

Asia WGS AF: 0.0530 AC: 184 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	6.1
DANN	Benign	0.28
PhyloP100		1.1
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: rs10488597; hg19: chr7-136560932;