rs978437

Variant names:

• chr7-136929431-C-T
• rs978437
• NM_001006630.2:c.-125+60013C>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+60013C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.67 in 151,886 control chromosomes in the GnomAD database, including 34,814 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 0.67 (34814 hom., cov: 30)
• Consequence: CHRM2 NM_001006630.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.81
• Publications: 8 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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.766 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHRM2	NM_001006630.2	c.-125+60013C>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+60013C>T		intron_variant	Intron 2 of 3		NM_001006630.2	ENSP00000505686.1

Frequencies

GnomAD3 genomes AF: 0.670 AC: 101610 AN: 151768 Hom.: 34758 Cov.: 30

Gnomad AFR AF: 0.773

Gnomad AMI AF: 0.612

Gnomad AMR AF: 0.534

Gnomad ASJ AF: 0.665

Gnomad EAS AF: 0.417

Gnomad SAS AF: 0.516

Gnomad FIN AF: 0.683

Gnomad MID AF: 0.579

Gnomad NFE AF: 0.667

Gnomad OTH AF: 0.660

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

GnomAD4 genome AF: 0.670 AC: 101715 AN: 151886 Hom.: 34814 Cov.: 30 AF XY: 0.665 AC XY: 49334 AN XY: 74216

African (AFR) AF: 0.773 AC: 32017 AN: 41408

American (AMR) AF: 0.533 AC: 8125 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.665 AC: 2306 AN: 3470

East Asian (EAS) AF: 0.417 AC: 2140 AN: 5134

South Asian (SAS) AF: 0.516 AC: 2485 AN: 4818

European-Finnish (FIN) AF: 0.683 AC: 7210 AN: 10556

Middle Eastern (MID) AF: 0.585 AC: 172 AN: 294

European-Non Finnish (NFE) AF: 0.667 AC: 45306 AN: 67932

Other (OTH) AF: 0.663 AC: 1397 AN: 2108

Alfa AF: 0.682 Hom.: 4620

Bravo AF: 0.660

Asia WGS AF: 0.512 AC: 1778 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.0040
DANN	Benign	0.17
PhyloP100		-2.8
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: rs978437; hg19: chr7-136614178;