rs324650

Variant names:

• chr7-137008914-T-A
• rs324650
• NM_001006630.2:c.-46-5906T>A

Variant summary

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

The NM_001006630.2(CHRM2):​c.-46-5906T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.538 in 151,828 control chromosomes in the GnomAD database, including 23,372 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 0.54 (23372 hom., cov: 32)
• Consequence: CHRM2 NM_001006630.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0300
• Publications: 38 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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.666 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHRM2	NM_001006630.2	c.-46-5906T>A		intron_variant	Intron 3 of 3	ENST00000680005.1	NP_001006631.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHRM2	ENST00000680005.1	c.-46-5906T>A		intron_variant	Intron 3 of 3		NM_001006630.2	ENSP00000505686.1

Frequencies

GnomAD3 genomes AF: 0.538 AC: 81663 AN: 151710 Hom.: 23333 Cov.: 32

Gnomad AFR AF: 0.672

Gnomad AMI AF: 0.545

Gnomad AMR AF: 0.411

Gnomad ASJ AF: 0.568

Gnomad EAS AF: 0.0818

Gnomad SAS AF: 0.250

Gnomad FIN AF: 0.577

Gnomad MID AF: 0.595

Gnomad NFE AF: 0.532

Gnomad OTH AF: 0.544

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

GnomAD4 genome AF: 0.538 AC: 81744 AN: 151828 Hom.: 23372 Cov.: 32 AF XY: 0.532 AC XY: 39434 AN XY: 74178

African (AFR) AF: 0.673 AC: 27876 AN: 41424

American (AMR) AF: 0.410 AC: 6241 AN: 15224

Ashkenazi Jewish (ASJ) AF: 0.568 AC: 1972 AN: 3472

East Asian (EAS) AF: 0.0816 AC: 420 AN: 5148

South Asian (SAS) AF: 0.251 AC: 1209 AN: 4824

European-Finnish (FIN) AF: 0.577 AC: 6089 AN: 10552

Middle Eastern (MID) AF: 0.588 AC: 173 AN: 294

European-Non Finnish (NFE) AF: 0.532 AC: 36134 AN: 67872

Other (OTH) AF: 0.538 AC: 1135 AN: 2110

Alfa AF: 0.548 Hom.: 2882

Bravo AF: 0.533

Asia WGS AF: 0.224 AC: 779 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.97
DANN	Benign	0.72
PhyloP100		0.030
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: rs324650; hg19: chr7-136693661;