rs324584

Variant names:

• chr7-136966132-G-A
• rs324584
• NM_001006630.2:c.-124-26055G>A

Your query was ambiguous. Multiple possible variants found:

• chr7-136966132-G-A
• chr7-136966132-G-C
• chr7-136966132-G-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.-124-26055G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.883 in 151,544 control chromosomes in the GnomAD database, including 59,547 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 0.88 (59547 hom., cov: 30)
• Consequence: CHRM2 NM_001006630.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0420
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.93 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHRM2	NM_001006630.2	c.-124-26055G>A		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.-124-26055G>A		intron_variant	Intron 2 of 3		NM_001006630.2	ENSP00000505686.1

Frequencies

GnomAD3 genomes AF: 0.883 AC: 133780 AN: 151424 Hom.: 59529 Cov.: 30

Gnomad AFR AF: 0.820

Gnomad AMI AF: 0.943

Gnomad AMR AF: 0.806

Gnomad ASJ AF: 0.975

Gnomad EAS AF: 0.713

Gnomad SAS AF: 0.843

Gnomad FIN AF: 0.968

Gnomad MID AF: 0.972

Gnomad NFE AF: 0.936

Gnomad OTH AF: 0.890

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

GnomAD4 genome AF: 0.883 AC: 133844 AN: 151544 Hom.: 59547 Cov.: 30 AF XY: 0.884 AC XY: 65512 AN XY: 74096

African (AFR) AF: 0.820 AC: 33962 AN: 41440

American (AMR) AF: 0.805 AC: 12247 AN: 15216

Ashkenazi Jewish (ASJ) AF: 0.975 AC: 3379 AN: 3466

East Asian (EAS) AF: 0.712 AC: 3663 AN: 5144

South Asian (SAS) AF: 0.843 AC: 4060 AN: 4816

European-Finnish (FIN) AF: 0.968 AC: 10137 AN: 10474

Middle Eastern (MID) AF: 0.969 AC: 285 AN: 294

European-Non Finnish (NFE) AF: 0.936 AC: 63384 AN: 67684

Other (OTH) AF: 0.890 AC: 1869 AN: 2100

Alfa AF: 0.907 Hom.: 7665

Bravo AF: 0.866

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.7
DANN	Benign	0.23
PhyloP100		0.042
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: rs324584; hg19: chr7-136650879;