rs324627

Variant names:

• chr7-136984904-G-A
• rs324627
• NM_001006630.2:c.-124-7283G>A

Your query was ambiguous. Multiple possible variants found:

• chr7-136984904-G-A
• chr7-136984904-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.-124-7283G>A 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 152,150 control chromosomes in the GnomAD database, including 56,421 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 (56421 hom., cov: 31)
• Consequence: CHRM2 NM_001006630.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.612
• 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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.929 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHRM2	NM_001006630.2	c.-124-7283G>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.-124-7283G>A		intron_variant	Intron 2 of 3		NM_001006630.2	ENSP00000505686.1

Frequencies

GnomAD3 genomes AF: 0.855 AC: 130013 AN: 152032 Hom.: 56415 Cov.: 31

Gnomad AFR AF: 0.726

Gnomad AMI AF: 0.943

Gnomad AMR AF: 0.796

Gnomad ASJ AF: 0.975

Gnomad EAS AF: 0.695

Gnomad SAS AF: 0.830

Gnomad FIN AF: 0.967

Gnomad MID AF: 0.971

Gnomad NFE AF: 0.935

Gnomad OTH AF: 0.869

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

GnomAD4 genome AF: 0.855 AC: 130051 AN: 152150 Hom.: 56421 Cov.: 31 AF XY: 0.857 AC XY: 63747 AN XY: 74386

African (AFR) AF: 0.725 AC: 30091 AN: 41490

American (AMR) AF: 0.795 AC: 12145 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.975 AC: 3385 AN: 3472

East Asian (EAS) AF: 0.694 AC: 3569 AN: 5144

South Asian (SAS) AF: 0.830 AC: 3993 AN: 4810

European-Finnish (FIN) AF: 0.967 AC: 10262 AN: 10610

Middle Eastern (MID) AF: 0.969 AC: 283 AN: 292

European-Non Finnish (NFE) AF: 0.935 AC: 63627 AN: 68028

Other (OTH) AF: 0.869 AC: 1836 AN: 2112

Alfa AF: 0.870 Hom.: 9506

Bravo AF: 0.833

Asia WGS AF: 0.779 AC: 2711 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.2
DANN	Benign	0.34
PhyloP100		0.61
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: rs324627; hg19: chr7-136669651;