chr7-136925178-C-T

Variant names:

• chr7-136925178-C-T
• rs1364407
• NM_001006630.2:c.-125+55760C>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+55760C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.668 in 152,022 control chromosomes in the GnomAD database, including 34,618 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 (34618 hom., cov: 32)
• Consequence: CHRM2 NM_001006630.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.07
• Publications: 4 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.761 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHRM2	NM_001006630.2	c.-125+55760C>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+55760C>T		intron_variant	Intron 2 of 3		NM_001006630.2	ENSP00000505686.1

Frequencies

GnomAD3 genomes AF: 0.668 AC: 101410 AN: 151904 Hom.: 34562 Cov.: 32

Gnomad AFR AF: 0.768

Gnomad AMI AF: 0.581

Gnomad AMR AF: 0.533

Gnomad ASJ AF: 0.665

Gnomad EAS AF: 0.418

Gnomad SAS AF: 0.517

Gnomad FIN AF: 0.681

Gnomad MID AF: 0.579

Gnomad NFE AF: 0.666

Gnomad OTH AF: 0.656

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

GnomAD4 genome AF: 0.668 AC: 101515 AN: 152022 Hom.: 34618 Cov.: 32 AF XY: 0.663 AC XY: 49236 AN XY: 74294

African (AFR) AF: 0.769 AC: 31903 AN: 41510

American (AMR) AF: 0.532 AC: 8114 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.665 AC: 2307 AN: 3470

East Asian (EAS) AF: 0.417 AC: 2148 AN: 5150

South Asian (SAS) AF: 0.517 AC: 2486 AN: 4810

European-Finnish (FIN) AF: 0.681 AC: 7191 AN: 10554

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

European-Non Finnish (NFE) AF: 0.666 AC: 45273 AN: 67946

Other (OTH) AF: 0.659 AC: 1391 AN: 2112

Alfa AF: 0.656 Hom.: 61846

Bravo AF: 0.658

Asia WGS AF: 0.511 AC: 1777 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.81
DANN	Benign	0.41
PhyloP100		-1.1
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: rs1364407; hg19: chr7-136609925;