rs324624

Variant names:

• chr7-136984489-A-G
• rs324624
• NM_001006630.2:c.-124-7698A>G

Your query was ambiguous. Multiple possible variants found:

• chr7-136984489-A-G
• chr7-136984489-A-T

Variant summary

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

The NM_001006630.2(CHRM2):​c.-124-7698A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.855 in 150,934 control chromosomes in the GnomAD database, including 55,904 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 0.85 (55904 hom., cov: 29)
• Consequence: CHRM2 NM_001006630.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.584
• Publications: 1 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=-1.01).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.929 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHRM2	NM_001006630.2	MANE Select	c.-124-7698A>G		intron	N/A	NP_001006631.1	P08172
	CHRM2	NM_000739.3		c.-124-7698A>G		intron	N/A	NP_000730.1	P08172
	CHRM2	NM_001006626.3		c.-124-7698A>G		intron	N/A	NP_001006627.1	A4D1Q0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHRM2	ENST00000680005.1	MANE Select	c.-124-7698A>G		intron	N/A	ENSP00000505686.1	P08172
	CHRM2	ENST00000320658.9	TSL:1	c.-46-30331A>G		intron	N/A	ENSP00000319984.5	P08172
	CHRM2	ENST00000401861.1	TSL:1	c.-124-7698A>G		intron	N/A	ENSP00000384401.1	P08172

Frequencies

GnomAD3 genomes AF: 0.855 AC: 128998 AN: 150836 Hom.: 55900 Cov.: 29

Gnomad AFR AF: 0.725

Gnomad AMI AF: 0.943

Gnomad AMR AF: 0.796

Gnomad ASJ AF: 0.975

Gnomad EAS AF: 0.695

Gnomad SAS AF: 0.839

Gnomad FIN AF: 0.965

Gnomad MID AF: 0.971

Gnomad NFE AF: 0.935

Gnomad OTH AF: 0.870

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

GnomAD4 genome AF: 0.855 AC: 129030 AN: 150934 Hom.: 55904 Cov.: 29 AF XY: 0.857 AC XY: 63174 AN XY: 73698

African (AFR) AF: 0.725 AC: 29791 AN: 41086

American (AMR) AF: 0.795 AC: 12062 AN: 15170

Ashkenazi Jewish (ASJ) AF: 0.975 AC: 3370 AN: 3458

East Asian (EAS) AF: 0.695 AC: 3539 AN: 5094

South Asian (SAS) AF: 0.840 AC: 4001 AN: 4764

European-Finnish (FIN) AF: 0.965 AC: 10051 AN: 10414

Middle Eastern (MID) AF: 0.969 AC: 279 AN: 288

European-Non Finnish (NFE) AF: 0.935 AC: 63277 AN: 67678

Other (OTH) AF: 0.870 AC: 1804 AN: 2074

Alfa AF: 0.892 Hom.: 7598

Bravo AF: 0.833

Asia WGS AF: 0.783 AC: 2723 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.5
DANN	Benign	0.31
PhyloP100		-0.58
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: rs324624; hg19: chr7-136669236;