rs1158586

Variant names:

• chr7-136952389-G-A
• rs1158586
• NM_001006630.2:c.-124-39798G>A

Your query was ambiguous. Multiple possible variants found:

• chr7-136952389-G-A
• chr7-136952389-G-C
• chr7-136952389-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001006630.2(CHRM2):​c.-124-39798G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.648 in 151,856 control chromosomes in the GnomAD database, including 32,354 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 0.65 (32354 hom., cov: 31)
• Consequence: CHRM2 NM_001006630.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.759
• Publications: 1 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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.702 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHRM2	NM_001006630.2	c.-124-39798G>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.-124-39798G>A		intron_variant	Intron 2 of 3		NM_001006630.2	ENSP00000505686.1

Frequencies

GnomAD3 genomes AF: 0.648 AC: 98276 AN: 151740 Hom.: 32324 Cov.: 31

Gnomad AFR AF: 0.709

Gnomad AMI AF: 0.581

Gnomad AMR AF: 0.520

Gnomad ASJ AF: 0.663

Gnomad EAS AF: 0.461

Gnomad SAS AF: 0.484

Gnomad FIN AF: 0.673

Gnomad MID AF: 0.589

Gnomad NFE AF: 0.661

Gnomad OTH AF: 0.643

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

GnomAD4 genome AF: 0.648 AC: 98352 AN: 151856 Hom.: 32354 Cov.: 31 AF XY: 0.643 AC XY: 47694 AN XY: 74200

African (AFR) AF: 0.709 AC: 29379 AN: 41430

American (AMR) AF: 0.519 AC: 7899 AN: 15230

Ashkenazi Jewish (ASJ) AF: 0.663 AC: 2299 AN: 3470

East Asian (EAS) AF: 0.460 AC: 2361 AN: 5128

South Asian (SAS) AF: 0.484 AC: 2333 AN: 4818

European-Finnish (FIN) AF: 0.673 AC: 7098 AN: 10544

Middle Eastern (MID) AF: 0.596 AC: 174 AN: 292

European-Non Finnish (NFE) AF: 0.661 AC: 44913 AN: 67916

Other (OTH) AF: 0.646 AC: 1366 AN: 2116

Alfa AF: 0.559 Hom.: 2442

Bravo AF: 0.638

Asia WGS AF: 0.503 AC: 1751 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.060
DANN	Benign	0.55
PhyloP100		-0.76
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: rs1158586; hg19: chr7-136637136;