rs324579

Variant names:

• chr7-136963965-G-A
• rs324579
• NM_001006630.2:c.-124-28222G>A

Your query was ambiguous. Multiple possible variants found:

• chr7-136963965-G-A
• chr7-136963965-G-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.-124-28222G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.85 in 152,064 control chromosomes in the GnomAD database, including 55,867 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 (55867 hom., cov: 31)
• Consequence: CHRM2 NM_001006630.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.214
• 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=-0.98).
• 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.-124-28222G>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.-124-28222G>A		intron_variant	Intron 2 of 3		NM_001006630.2	ENSP00000505686.1

Frequencies

GnomAD3 genomes AF: 0.851 AC: 129238 AN: 151946 Hom.: 55860 Cov.: 31

Gnomad AFR AF: 0.728

Gnomad AMI AF: 0.943

Gnomad AMR AF: 0.743

Gnomad ASJ AF: 0.975

Gnomad EAS AF: 0.688

Gnomad SAS AF: 0.829

Gnomad FIN AF: 0.968

Gnomad MID AF: 0.968

Gnomad NFE AF: 0.936

Gnomad OTH AF: 0.862

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

GnomAD4 genome AF: 0.850 AC: 129276 AN: 152064 Hom.: 55867 Cov.: 31 AF XY: 0.852 AC XY: 63333 AN XY: 74362

African (AFR) AF: 0.728 AC: 30155 AN: 41428

American (AMR) AF: 0.742 AC: 11321 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.975 AC: 3383 AN: 3470

East Asian (EAS) AF: 0.688 AC: 3533 AN: 5138

South Asian (SAS) AF: 0.829 AC: 3997 AN: 4820

European-Finnish (FIN) AF: 0.968 AC: 10270 AN: 10612

Middle Eastern (MID) AF: 0.966 AC: 284 AN: 294

European-Non Finnish (NFE) AF: 0.936 AC: 63650 AN: 68012

Other (OTH) AF: 0.862 AC: 1823 AN: 2114

Alfa AF: 0.894 Hom.: 3112

Bravo AF: 0.824

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	3.3
DANN	Benign	0.41
PhyloP100		0.21
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: rs324579; hg19: chr7-136648712;