rs324584

Positions:

• chr7-136966132-G-A
• chr7-136966132-G-C
• chr7-136966132-G-T

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
CHRM2	NM_001006630.2	c.-124-26055G>A		intron_variant		ENST00000680005.1	NP_001006631.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHRM2	ENST00000680005.1	c.-124-26055G>A		intron_variant			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

Gnomad4 AFR AF: 0.820

Gnomad4 AMR AF: 0.805

Gnomad4 ASJ AF: 0.975

Gnomad4 EAS AF: 0.712

Gnomad4 SAS AF: 0.843

Gnomad4 FIN AF: 0.968

Gnomad4 NFE AF: 0.936

Gnomad4 OTH AF: 0.890

Alfa AF: 0.911 Hom.: 7407

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs324584; hg19: chr7-136650879;