rs6947206

Positions:

• chr7-136930364-C-G

Variant summary

Our verdict is Benign. Variant got -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

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
CHRM2	NM_001006630.2	c.-125+60946C>G		intron_variant		ENST00000680005.1
LOC349160	NR_046103.1	n.342-28363G>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHRM2	ENST00000680005.1	c.-125+60946C>G		intron_variant			NM_001006630.2	P1
	ENST00000586239.5	n.273+102430G>C		intron_variant, non_coding_transcript_variant		5

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

Gnomad4 AFR AF: 0.735

Gnomad4 AMR AF: 0.395

Gnomad4 ASJ AF: 0.526

Gnomad4 EAS AF: 0.0410

Gnomad4 SAS AF: 0.211

Gnomad4 FIN AF: 0.490

Gnomad4 NFE AF: 0.514

Gnomad4 OTH AF: 0.518

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs6947206; hg19: chr7-136615111;