NM_001006630.2:c.-124-52801T>C

Variant names:

• chr7-136939386-T-C
• rs7782965
• NM_001006630.2:c.-124-52801T>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.-124-52801T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.674 in 152,126 control chromosomes in the GnomAD database, including 35,336 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 0.67 (35336 hom., cov: 33)
• Consequence: CHRM2 NM_001006630.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.160
• 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=-0.79).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.763 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHRM2	NM_001006630.2	c.-124-52801T>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.-124-52801T>C		intron_variant	Intron 2 of 3		NM_001006630.2	ENSP00000505686.1

Frequencies

GnomAD3 genomes AF: 0.674 AC: 102494 AN: 152008 Hom.: 35280 Cov.: 33

Gnomad AFR AF: 0.769

Gnomad AMI AF: 0.612

Gnomad AMR AF: 0.538

Gnomad ASJ AF: 0.672

Gnomad EAS AF: 0.421

Gnomad SAS AF: 0.521

Gnomad FIN AF: 0.685

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.677

Gnomad OTH AF: 0.667

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

GnomAD4 genome AF: 0.674 AC: 102600 AN: 152126 Hom.: 35336 Cov.: 33 AF XY: 0.669 AC XY: 49786 AN XY: 74392

African (AFR) AF: 0.770 AC: 31961 AN: 41502

American (AMR) AF: 0.537 AC: 8199 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.672 AC: 2334 AN: 3472

East Asian (EAS) AF: 0.421 AC: 2177 AN: 5174

South Asian (SAS) AF: 0.522 AC: 2518 AN: 4822

European-Finnish (FIN) AF: 0.685 AC: 7251 AN: 10590

Middle Eastern (MID) AF: 0.609 AC: 179 AN: 294

European-Non Finnish (NFE) AF: 0.677 AC: 46007 AN: 67964

Other (OTH) AF: 0.670 AC: 1416 AN: 2114

Alfa AF: 0.624 Hom.: 2250

Bravo AF: 0.665

Asia WGS AF: 0.516 AC: 1794 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	1.9
DANN	Benign	0.74
PhyloP100		-0.16
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: rs7782965; hg19: chr7-136624133;