rs2061174

Variant names:

• chr7-136976653-G-A
• rs2061174
• NM_001006630.2:c.-124-15534G>A

Your query was ambiguous. Multiple possible variants found:

• chr7-136976653-G-A
• chr7-136976653-G-C
• chr7-136976653-G-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.-124-15534G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.601 in 152,008 control chromosomes in the GnomAD database, including 28,459 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 0.60 (28459 hom., cov: 31)
• Consequence: CHRM2 NM_001006630.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0910
• Publications: 25 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 = 0.671 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001006630.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHRM2	NM_001006630.2	MANE Select	c.-124-15534G>A		intron	N/A	NP_001006631.1
	CHRM2	NM_000739.3		c.-124-15534G>A		intron	N/A	NP_000730.1
	CHRM2	NM_001006626.3		c.-124-15534G>A		intron	N/A	NP_001006627.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHRM2	ENST00000680005.1	MANE Select	c.-124-15534G>A		intron	N/A	ENSP00000505686.1
	CHRM2	ENST00000320658.9	TSL:1	c.-46-38167G>A		intron	N/A	ENSP00000319984.5
	CHRM2	ENST00000401861.1	TSL:1	c.-124-15534G>A		intron	N/A	ENSP00000384401.1

Frequencies

GnomAD3 genomes AF: 0.601 AC: 91325 AN: 151890 Hom.: 28440 Cov.: 31

Gnomad AFR AF: 0.488

Gnomad AMI AF: 0.601

Gnomad AMR AF: 0.527

Gnomad ASJ AF: 0.715

Gnomad EAS AF: 0.361

Gnomad SAS AF: 0.526

Gnomad FIN AF: 0.779

Gnomad MID AF: 0.646

Gnomad NFE AF: 0.676

Gnomad OTH AF: 0.620

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

GnomAD4 genome AF: 0.601 AC: 91372 AN: 152008 Hom.: 28459 Cov.: 31 AF XY: 0.605 AC XY: 44973 AN XY: 74292

African (AFR) AF: 0.488 AC: 20207 AN: 41426

American (AMR) AF: 0.526 AC: 8031 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.715 AC: 2482 AN: 3472

East Asian (EAS) AF: 0.362 AC: 1870 AN: 5162

South Asian (SAS) AF: 0.526 AC: 2534 AN: 4816

European-Finnish (FIN) AF: 0.779 AC: 8250 AN: 10590

Middle Eastern (MID) AF: 0.650 AC: 191 AN: 294

European-Non Finnish (NFE) AF: 0.676 AC: 45941 AN: 67950

Other (OTH) AF: 0.623 AC: 1318 AN: 2116

Alfa AF: 0.635 Hom.: 47863

Bravo AF: 0.575

Asia WGS AF: 0.466 AC: 1621 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.26
DANN	Benign	0.44
PhyloP100		-0.091
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: rs2061174; hg19: chr7-136661400; COSMIC: COSV108138354;