rs17411478

Variant names:

• chr7-136916210-C-T
• rs17411478
• NM_001006630.2:c.-125+46792C>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.-125+46792C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.223 in 151,688 control chromosomes in the GnomAD database, including 4,924 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 (4924 hom., cov: 31)
• Consequence: CHRM2 NM_001006630.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.290
• Publications: 3 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=-0.98).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.319 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHRM2	NM_001006630.2	c.-125+46792C>T		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+46792C>T		intron_variant	Intron 2 of 3		NM_001006630.2	ENSP00000505686.1

Frequencies

GnomAD3 genomes AF: 0.223 AC: 33857 AN: 151568 Hom.: 4925 Cov.: 31

Gnomad AFR AF: 0.0634

Gnomad AMI AF: 0.211

Gnomad AMR AF: 0.227

Gnomad ASJ AF: 0.291

Gnomad EAS AF: 0.0394

Gnomad SAS AF: 0.131

Gnomad FIN AF: 0.307

Gnomad MID AF: 0.301

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: 0.223 AC: 33849 AN: 151688 Hom.: 4924 Cov.: 31 AF XY: 0.220 AC XY: 16334 AN XY: 74116

African (AFR) AF: 0.0634 AC: 2627 AN: 41458

American (AMR) AF: 0.227 AC: 3448 AN: 15204

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

East Asian (EAS) AF: 0.0389 AC: 200 AN: 5140

South Asian (SAS) AF: 0.131 AC: 632 AN: 4816

European-Finnish (FIN) AF: 0.307 AC: 3235 AN: 10536

Middle Eastern (MID) AF: 0.299 AC: 88 AN: 294

European-Non Finnish (NFE) AF: 0.323 AC: 21881 AN: 67766

Other (OTH) AF: 0.256 AC: 537 AN: 2100

Alfa AF: 0.253 Hom.: 983

Bravo AF: 0.210

Asia WGS AF: 0.0960 AC: 335 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	2.3
DANN	Benign	0.29
PhyloP100		-0.29
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: rs17411478; hg19: chr7-136600957;