rs324614

chr7-136979227-G-Cchr7-136979227-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.-124-12960G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.246 in 152,074 control chromosomes in the GnomAD database, including 4,751 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 0.25 (4751 hom., cov: 33)
• Consequence: CHRM2 NM_001006630.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.669

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.316 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHRM2	NM_001006630.2	c.-124-12960G>C		intron_variant		ENST00000680005.1
LOC349160	NR_046103.1	n.341+53567C>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHRM2	ENST00000680005.1	c.-124-12960G>C		intron_variant			NM_001006630.2	P1
	ENST00000586239.5	n.273+53567C>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.246 AC: 37443 AN: 151954 Hom.: 4753 Cov.: 33

Gnomad AFR AF: 0.212

Gnomad AMI AF: 0.344

Gnomad AMR AF: 0.220

Gnomad ASJ AF: 0.304

Gnomad EAS AF: 0.330

Gnomad SAS AF: 0.313

Gnomad FIN AF: 0.191

Gnomad MID AF: 0.345

Gnomad NFE AF: 0.266

Gnomad OTH AF: 0.241

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

GnomAD4 genome AF: 0.246 AC: 37435 AN: 152074 Hom.: 4751 Cov.: 33 AF XY: 0.244 AC XY: 18154 AN XY: 74346

Gnomad4 AFR AF: 0.212

Gnomad4 AMR AF: 0.219

Gnomad4 ASJ AF: 0.304

Gnomad4 EAS AF: 0.329

Gnomad4 SAS AF: 0.314

Gnomad4 FIN AF: 0.191

Gnomad4 NFE AF: 0.266

Gnomad4 OTH AF: 0.239

Alfa AF: 0.250 Hom.: 598

Bravo AF: 0.246

Asia WGS AF: 0.318 AC: 1106 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.60
Dann	Benign	0.51

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: rs324614; hg19: chr7-136663974;