rs1424387

Variant names:

• chr7-136904863-G-C
• rs1424387
• NM_001006630.2:c.-125+35445G>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.-125+35445G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.223 in 151,728 control chromosomes in the GnomAD database, including 4,930 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 0.22 (4930 hom., cov: 32)
• Consequence: CHRM2 NM_001006630.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.847
• Publications: 5 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 = 0.32 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHRM2	NM_001006630.2	c.-125+35445G>C		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.-125+35445G>C		intron_variant	Intron 2 of 3		NM_001006630.2	ENSP00000505686.1

Frequencies

GnomAD3 genomes AF: 0.223 AC: 33814 AN: 151608 Hom.: 4931 Cov.: 32

Gnomad AFR AF: 0.0614

Gnomad AMI AF: 0.211

Gnomad AMR AF: 0.227

Gnomad ASJ AF: 0.293

Gnomad EAS AF: 0.0396

Gnomad SAS AF: 0.130

Gnomad FIN AF: 0.307

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.323

Gnomad OTH AF: 0.257

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

GnomAD4 genome AF: 0.223 AC: 33799 AN: 151728 Hom.: 4930 Cov.: 32 AF XY: 0.220 AC XY: 16313 AN XY: 74158

African (AFR) AF: 0.0612 AC: 2539 AN: 41474

American (AMR) AF: 0.227 AC: 3452 AN: 15200

Ashkenazi Jewish (ASJ) AF: 0.293 AC: 1013 AN: 3462

East Asian (EAS) AF: 0.0391 AC: 201 AN: 5140

South Asian (SAS) AF: 0.130 AC: 628 AN: 4818

European-Finnish (FIN) AF: 0.307 AC: 3226 AN: 10516

Middle Eastern (MID) AF: 0.299 AC: 88 AN: 294

European-Non Finnish (NFE) AF: 0.323 AC: 21925 AN: 67808

Other (OTH) AF: 0.254 AC: 535 AN: 2106

Alfa AF: 0.268 Hom.: 781

Bravo AF: 0.209

Asia WGS AF: 0.0970 AC: 338 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	1.0
DANN	Benign	0.76
PhyloP100		-0.85
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: rs1424387; hg19: chr7-136589610;