NM_001006630.2:c.-125+47178G>A

Variant names:

• chr7-136916596-G-A
• rs17496259
• NM_001006630.2:c.-125+47178G>A

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+47178G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.224 in 150,726 control chromosomes in the GnomAD database, including 4,933 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 (4933 hom., cov: 31)
• Consequence: CHRM2 NM_001006630.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0830
• Publications: 2 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.321 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHRM2	NM_001006630.2	c.-125+47178G>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+47178G>A		intron_variant	Intron 2 of 3		NM_001006630.2	ENSP00000505686.1

Frequencies

GnomAD3 genomes AF: 0.224 AC: 33774 AN: 150612 Hom.: 4934 Cov.: 31

Gnomad AFR AF: 0.0635

Gnomad AMI AF: 0.211

Gnomad AMR AF: 0.229

Gnomad ASJ AF: 0.291

Gnomad EAS AF: 0.0397

Gnomad SAS AF: 0.132

Gnomad FIN AF: 0.309

Gnomad MID AF: 0.303

Gnomad NFE AF: 0.324

Gnomad OTH AF: 0.259

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

GnomAD4 genome AF: 0.224 AC: 33766 AN: 150726 Hom.: 4933 Cov.: 31 AF XY: 0.221 AC XY: 16300 AN XY: 73614

African (AFR) AF: 0.0635 AC: 2618 AN: 41248

American (AMR) AF: 0.229 AC: 3448 AN: 15072

Ashkenazi Jewish (ASJ) AF: 0.291 AC: 1009 AN: 3462

East Asian (EAS) AF: 0.0392 AC: 201 AN: 5126

South Asian (SAS) AF: 0.132 AC: 632 AN: 4802

European-Finnish (FIN) AF: 0.309 AC: 3127 AN: 10128

Middle Eastern (MID) AF: 0.301 AC: 88 AN: 292

European-Non Finnish (NFE) AF: 0.324 AC: 21914 AN: 67590

Other (OTH) AF: 0.256 AC: 537 AN: 2096

Alfa AF: 0.260 Hom.: 791

Bravo AF: 0.210

Asia WGS AF: 0.0940 AC: 327 AN: 3456

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.4
DANN	Benign	0.68
PhyloP100		-0.083
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: rs17496259; hg19: chr7-136601343;