rs4475425

Variant names:

• chr7-136890452-G-A
• rs4475425
• NM_001006630.2:c.-125+21034G>A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001006630.2(CHRM2):​c.-125+21034G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.304 in 152,094 control chromosomes in the GnomAD database, including 7,648 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 0.30 (7648 hom., cov: 33)
• Consequence: CHRM2 NM_001006630.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.470

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=-0.71).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.411 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHRM2	NM_001006630.2	c.-125+21034G>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.-125+21034G>A		intron_variant	Intron 2 of 3		NM_001006630.2	ENSP00000505686.1

Frequencies

GnomAD3 genomes AF: 0.303 AC: 46122 AN: 151976 Hom.: 7634 Cov.: 33

Gnomad AFR AF: 0.416

Gnomad AMI AF: 0.274

Gnomad AMR AF: 0.226

Gnomad ASJ AF: 0.284

Gnomad EAS AF: 0.414

Gnomad SAS AF: 0.342

Gnomad FIN AF: 0.301

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.244

Gnomad OTH AF: 0.269

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

GnomAD4 genome AF: 0.304 AC: 46176 AN: 152094 Hom.: 7648 Cov.: 33 AF XY: 0.307 AC XY: 22837 AN XY: 74334

Gnomad4 AFR AF: 0.416

Gnomad4 AMR AF: 0.226

Gnomad4 ASJ AF: 0.284

Gnomad4 EAS AF: 0.414

Gnomad4 SAS AF: 0.343

Gnomad4 FIN AF: 0.301

Gnomad4 NFE AF: 0.244

Gnomad4 OTH AF: 0.277

Alfa AF: 0.254 Hom.: 6730

Bravo AF: 0.300

Asia WGS AF: 0.393 AC: 1364 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	7.3
DANN	Benign	0.46

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: rs4475425; hg19: chr7-136575199; COSMIC: COSV57768492;