7-136913540-C-T

Variant names:

• chr7-136913540-C-T
• rs1364404
• NM_001006630.2:c.-125+44122C>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+44122C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.251 in 151,818 control chromosomes in the GnomAD database, including 5,418 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 0.25 (5418 hom., cov: 32)
• Consequence: CHRM2 NM_001006630.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.567
• Publications: 2 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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.32 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHRM2	NM_001006630.2	c.-125+44122C>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+44122C>T		intron_variant	Intron 2 of 3		NM_001006630.2	ENSP00000505686.1

Frequencies

GnomAD3 genomes AF: 0.251 AC: 38151 AN: 151700 Hom.: 5420 Cov.: 32

Gnomad AFR AF: 0.159

Gnomad AMI AF: 0.211

Gnomad AMR AF: 0.237

Gnomad ASJ AF: 0.293

Gnomad EAS AF: 0.0404

Gnomad SAS AF: 0.136

Gnomad FIN AF: 0.306

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.324

Gnomad OTH AF: 0.280

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

GnomAD4 genome AF: 0.251 AC: 38157 AN: 151818 Hom.: 5418 Cov.: 32 AF XY: 0.247 AC XY: 18327 AN XY: 74184

African (AFR) AF: 0.160 AC: 6614 AN: 41464

American (AMR) AF: 0.237 AC: 3596 AN: 15194

Ashkenazi Jewish (ASJ) AF: 0.293 AC: 1017 AN: 3470

East Asian (EAS) AF: 0.0399 AC: 205 AN: 5140

South Asian (SAS) AF: 0.136 AC: 657 AN: 4832

European-Finnish (FIN) AF: 0.306 AC: 3239 AN: 10570

Middle Eastern (MID) AF: 0.306 AC: 90 AN: 294

European-Non Finnish (NFE) AF: 0.324 AC: 21965 AN: 67838

Other (OTH) AF: 0.277 AC: 582 AN: 2104

Alfa AF: 0.278 Hom.: 829

Bravo AF: 0.241

Asia WGS AF: 0.105 AC: 367 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.2
DANN	Benign	0.19
PhyloP100		-0.57
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: rs1364404; hg19: chr7-136598287;