rs6947206

Variant names:

• chr7-136930364-C-G
• rs6947206
• NM_001006630.2:c.-125+60946C>G

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+60946C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.536 in 151,790 control chromosomes in the GnomAD database, including 23,766 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 0.54 (23766 hom., cov: 31)
• Consequence: CHRM2 NM_001006630.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.176
• 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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.728 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHRM2	NM_001006630.2	c.-125+60946C>G		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+60946C>G		intron_variant	Intron 2 of 3		NM_001006630.2	ENSP00000505686.1

Frequencies

GnomAD3 genomes AF: 0.535 AC: 81198 AN: 151672 Hom.: 23719 Cov.: 31

Gnomad AFR AF: 0.734

Gnomad AMI AF: 0.505

Gnomad AMR AF: 0.396

Gnomad ASJ AF: 0.526

Gnomad EAS AF: 0.0415

Gnomad SAS AF: 0.212

Gnomad FIN AF: 0.490

Gnomad MID AF: 0.474

Gnomad NFE AF: 0.514

Gnomad OTH AF: 0.524

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

GnomAD4 genome AF: 0.536 AC: 81285 AN: 151790 Hom.: 23766 Cov.: 31 AF XY: 0.524 AC XY: 38855 AN XY: 74134

African (AFR) AF: 0.735 AC: 30428 AN: 41418

American (AMR) AF: 0.395 AC: 6028 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.526 AC: 1824 AN: 3468

East Asian (EAS) AF: 0.0410 AC: 208 AN: 5072

South Asian (SAS) AF: 0.211 AC: 1014 AN: 4804

European-Finnish (FIN) AF: 0.490 AC: 5171 AN: 10558

Middle Eastern (MID) AF: 0.476 AC: 139 AN: 292

European-Non Finnish (NFE) AF: 0.514 AC: 34920 AN: 67892

Other (OTH) AF: 0.518 AC: 1093 AN: 2110

Alfa AF: 0.537 Hom.: 2852

Bravo AF: 0.538

Asia WGS AF: 0.172 AC: 600 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	2.2
DANN	Benign	0.54
PhyloP100		0.18
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: rs6947206; hg19: chr7-136615111;