rs1469179

Variant names:

• chr7-136936930-A-T
• rs1469179
• NM_001006630.2:c.-124-55257A>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.-124-55257A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.522 in 151,940 control chromosomes in the GnomAD database, including 22,453 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 0.52 (22453 hom., cov: 32)
• Consequence: CHRM2 NM_001006630.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.142
• 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=-0.74).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.685 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHRM2	NM_001006630.2	c.-124-55257A>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.-124-55257A>T		intron_variant	Intron 2 of 3		NM_001006630.2	ENSP00000505686.1

Frequencies

GnomAD3 genomes AF: 0.522 AC: 79288 AN: 151820 Hom.: 22412 Cov.: 32

Gnomad AFR AF: 0.692

Gnomad AMI AF: 0.508

Gnomad AMR AF: 0.388

Gnomad ASJ AF: 0.527

Gnomad EAS AF: 0.0408

Gnomad SAS AF: 0.212

Gnomad FIN AF: 0.492

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.513

Gnomad OTH AF: 0.513

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

GnomAD4 genome AF: 0.522 AC: 79367 AN: 151940 Hom.: 22453 Cov.: 32 AF XY: 0.511 AC XY: 37976 AN XY: 74250

African (AFR) AF: 0.692 AC: 28712 AN: 41488

American (AMR) AF: 0.387 AC: 5913 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.527 AC: 1824 AN: 3464

East Asian (EAS) AF: 0.0403 AC: 208 AN: 5162

South Asian (SAS) AF: 0.211 AC: 1016 AN: 4820

European-Finnish (FIN) AF: 0.492 AC: 5175 AN: 10520

Middle Eastern (MID) AF: 0.469 AC: 138 AN: 294

European-Non Finnish (NFE) AF: 0.513 AC: 34850 AN: 67894

Other (OTH) AF: 0.507 AC: 1069 AN: 2110

Alfa AF: 0.529 Hom.: 2751

Bravo AF: 0.524

Asia WGS AF: 0.170 AC: 593 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	1.0
DANN	Benign	0.56
PhyloP100		-0.14
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: rs1469179; hg19: chr7-136621677;