rs1455858

Variant names:

• chr7-136946956-T-C
• rs1455858
• NM_001006630.2:c.-124-45231T>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.-124-45231T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.686 in 152,010 control chromosomes in the GnomAD database, including 36,645 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 0.69 (36645 hom., cov: 32)
• Consequence: CHRM2 NM_001006630.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.152
• Publications: 18 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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.812 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHRM2	NM_001006630.2	c.-124-45231T>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.-124-45231T>C		intron_variant	Intron 2 of 3		NM_001006630.2	ENSP00000505686.1

Frequencies

GnomAD3 genomes AF: 0.686 AC: 104124 AN: 151892 Hom.: 36594 Cov.: 32

Gnomad AFR AF: 0.819

Gnomad AMI AF: 0.611

Gnomad AMR AF: 0.535

Gnomad ASJ AF: 0.670

Gnomad EAS AF: 0.467

Gnomad SAS AF: 0.514

Gnomad FIN AF: 0.673

Gnomad MID AF: 0.617

Gnomad NFE AF: 0.671

Gnomad OTH AF: 0.675

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

GnomAD4 genome AF: 0.686 AC: 104225 AN: 152010 Hom.: 36645 Cov.: 32 AF XY: 0.680 AC XY: 50510 AN XY: 74310

African (AFR) AF: 0.819 AC: 33976 AN: 41470

American (AMR) AF: 0.534 AC: 8148 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.670 AC: 2324 AN: 3468

East Asian (EAS) AF: 0.466 AC: 2409 AN: 5164

South Asian (SAS) AF: 0.515 AC: 2484 AN: 4822

European-Finnish (FIN) AF: 0.673 AC: 7103 AN: 10552

Middle Eastern (MID) AF: 0.622 AC: 183 AN: 294

European-Non Finnish (NFE) AF: 0.671 AC: 45612 AN: 67960

Other (OTH) AF: 0.677 AC: 1430 AN: 2112

Alfa AF: 0.666 Hom.: 56676

Bravo AF: 0.680

Asia WGS AF: 0.527 AC: 1833 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.4
DANN	Benign	0.83
PhyloP100		-0.15
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: rs1455858; hg19: chr7-136631703;