rs10488602

Positions:

• chr7-137005756-T-C

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHRM2	NM_001006630.2	c.-46-9064T>C		intron_variant		ENST00000680005.1	NP_001006631.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHRM2	ENST00000680005.1	c.-46-9064T>C		intron_variant			NM_001006630.2	ENSP00000505686.1

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

Gnomad4 AFR AF: 0.0417

Gnomad4 AMR AF: 0.226

Gnomad4 ASJ AF: 0.172

Gnomad4 EAS AF: 0.440

Gnomad4 SAS AF: 0.272

Gnomad4 FIN AF: 0.178

Gnomad4 NFE AF: 0.196

Gnomad4 OTH AF: 0.177

Alfa AF: 0.191 Hom.: 3876

Bravo AF: 0.165

Asia WGS AF: 0.354 AC: 1230 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	14
DANN	Benign	0.70

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

LitVar

Other links and lift over

dbSNP: rs10488602; hg19: chr7-136690503;