rs2350782

Positions:

• chr7-136957887-T-C
• chr7-136957887-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001006630.2(CHRM2):​c.-124-34300T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.107 in 152,282 control chromosomes in the GnomAD database, including 1,297 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 0.11 (1297 hom., cov: 33)
• Consequence: CHRM2 NM_001006630.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.230

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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.37 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHRM2	NM_001006630.2	c.-124-34300T>C		intron_variant		ENST00000680005.1
LOC349160	NR_046103.1	n.342-55886A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHRM2	ENST00000680005.1	c.-124-34300T>C		intron_variant			NM_001006630.2	P1
	ENST00000586239.5	n.273+74907A>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.107 AC: 16325 AN: 152164 Hom.: 1291 Cov.: 33

Gnomad AFR AF: 0.0289

Gnomad AMI AF: 0.0592

Gnomad AMR AF: 0.116

Gnomad ASJ AF: 0.112

Gnomad EAS AF: 0.384

Gnomad SAS AF: 0.228

Gnomad FIN AF: 0.160

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.116

Gnomad OTH AF: 0.107

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

GnomAD4 genome AF: 0.107 AC: 16338 AN: 152282 Hom.: 1297 Cov.: 33 AF XY: 0.114 AC XY: 8479 AN XY: 74454

Gnomad4 AFR AF: 0.0288

Gnomad4 AMR AF: 0.116

Gnomad4 ASJ AF: 0.112

Gnomad4 EAS AF: 0.384

Gnomad4 SAS AF: 0.228

Gnomad4 FIN AF: 0.160

Gnomad4 NFE AF: 0.116

Gnomad4 OTH AF: 0.116

Alfa AF: 0.109 Hom.: 206

Bravo AF: 0.0992

Asia WGS AF: 0.285 AC: 988 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.5
DANN	Benign	0.72

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: rs2350782; hg19: chr7-136642634;