rs1364409

chr7-136927286-T-Achr7-136927286-T-Cchr7-136927286-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001006630.2(CHRM2):c.-125+57868T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.658 in 151,946 control chromosomes in the GnomAD database, including 33,573 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 0.66 (33573 hom., cov: 31)
• Consequence: CHRM2 NM_001006630.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.182

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.726 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHRM2	NM_001006630.2	c.-125+57868T>A		intron_variant		ENST00000680005.1
LOC349160	NR_046103.1	n.342-25285A>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHRM2	ENST00000680005.1	c.-125+57868T>A		intron_variant			NM_001006630.2	P1
	ENST00000586239.5	n.273+105508A>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.658 AC: 99955 AN: 151828 Hom.: 33524 Cov.: 31

Gnomad AFR AF: 0.733

Gnomad AMI AF: 0.581

Gnomad AMR AF: 0.529

Gnomad ASJ AF: 0.665

Gnomad EAS AF: 0.421

Gnomad SAS AF: 0.518

Gnomad FIN AF: 0.684

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.667

Gnomad OTH AF: 0.652

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

GnomAD4 genome AF: 0.658 AC: 100052 AN: 151946 Hom.: 33573 Cov.: 31 AF XY: 0.654 AC XY: 48563 AN XY: 74252

Gnomad4 AFR AF: 0.733

Gnomad4 AMR AF: 0.528

Gnomad4 ASJ AF: 0.665

Gnomad4 EAS AF: 0.421

Gnomad4 SAS AF: 0.518

Gnomad4 FIN AF: 0.684

Gnomad4 NFE AF: 0.667

Gnomad4 OTH AF: 0.655

Alfa AF: 0.576 Hom.: 1692

Bravo AF: 0.647

Asia WGS AF: 0.511 AC: 1776 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	0.73
Dann	Benign	0.49

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

Publications

LitVar

Other links and lift over

dbSNP: rs1364409; hg19: chr7-136612033;