rs17411561

Variant names:

• chr7-136916622-T-C
• rs17411561
• NM_001006630.2:c.-125+47204T>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.-125+47204T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.222 in 150,862 control chromosomes in the GnomAD database, including 4,866 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 (4866 hom., cov: 31)
• Consequence: CHRM2 NM_001006630.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.875
• 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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.32 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001006630.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHRM2	NM_001006630.2	MANE Select	c.-125+47204T>C		intron	N/A	NP_001006631.1
	CHRM2	NM_000739.3		c.-125+47204T>C		intron	N/A	NP_000730.1
	CHRM2	NM_001006626.3		c.-202-34381T>C		intron	N/A	NP_001006627.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHRM2	ENST00000680005.1	MANE Select	c.-125+47204T>C		intron	N/A	ENSP00000505686.1
	CHRM2	ENST00000320658.9	TSL:1	c.-47+47204T>C		intron	N/A	ENSP00000319984.5
	CHRM2	ENST00000401861.1	TSL:1	c.-202-34381T>C		intron	N/A	ENSP00000384401.1

Frequencies

GnomAD3 genomes AF: 0.223 AC: 33564 AN: 150754 Hom.: 4867 Cov.: 31

Gnomad AFR AF: 0.0615

Gnomad AMI AF: 0.211

Gnomad AMR AF: 0.228

Gnomad ASJ AF: 0.290

Gnomad EAS AF: 0.0395

Gnomad SAS AF: 0.130

Gnomad FIN AF: 0.304

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.323

Gnomad OTH AF: 0.259

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

GnomAD4 genome AF: 0.222 AC: 33549 AN: 150862 Hom.: 4866 Cov.: 31 AF XY: 0.220 AC XY: 16185 AN XY: 73702

African (AFR) AF: 0.0613 AC: 2536 AN: 41370

American (AMR) AF: 0.228 AC: 3444 AN: 15104

Ashkenazi Jewish (ASJ) AF: 0.290 AC: 1004 AN: 3462

East Asian (EAS) AF: 0.0390 AC: 201 AN: 5156

South Asian (SAS) AF: 0.130 AC: 629 AN: 4822

European-Finnish (FIN) AF: 0.304 AC: 3068 AN: 10092

Middle Eastern (MID) AF: 0.297 AC: 85 AN: 286

European-Non Finnish (NFE) AF: 0.323 AC: 21856 AN: 67576

Other (OTH) AF: 0.256 AC: 534 AN: 2082

Alfa AF: 0.260 Hom.: 788

Bravo AF: 0.209

Asia WGS AF: 0.0940 AC: 323 AN: 3438

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	5.8
DANN	Benign	0.35
PhyloP100		0.88
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: rs17411561; hg19: chr7-136601369;