rs324582

Positions:

• chr7-136965860-G-A
• chr7-136965860-G-C

Variant summary

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

The NM_001006630.2(CHRM2):​c.-124-26327G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.856 in 151,862 control chromosomes in the GnomAD database, including 56,452 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 0.86 (56452 hom., cov: 31)
• Consequence: CHRM2 NM_001006630.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.525

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 (NFE) allele frequency at 95% confidence interval = 0.93 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHRM2	NM_001006630.2	c.-124-26327G>A		intron_variant		ENST00000680005.1	NP_001006631.1
LOC349160	NR_046103.1	n.342-63859C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHRM2	ENST00000680005.1	c.-124-26327G>A		intron_variant			NM_001006630.2	ENSP00000505686	P1
	ENST00000586239.5	n.273+66934C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.856 AC: 129947 AN: 151744 Hom.: 56446 Cov.: 31

Gnomad AFR AF: 0.727

Gnomad AMI AF: 0.943

Gnomad AMR AF: 0.797

Gnomad ASJ AF: 0.975

Gnomad EAS AF: 0.700

Gnomad SAS AF: 0.838

Gnomad FIN AF: 0.967

Gnomad MID AF: 0.968

Gnomad NFE AF: 0.936

Gnomad OTH AF: 0.871

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

GnomAD4 genome AF: 0.856 AC: 129985 AN: 151862 Hom.: 56452 Cov.: 31 AF XY: 0.858 AC XY: 63715 AN XY: 74230

Gnomad4 AFR AF: 0.727

Gnomad4 AMR AF: 0.795

Gnomad4 ASJ AF: 0.975

Gnomad4 EAS AF: 0.699

Gnomad4 SAS AF: 0.839

Gnomad4 FIN AF: 0.967

Gnomad4 NFE AF: 0.936

Gnomad4 OTH AF: 0.871

Alfa AF: 0.911 Hom.: 28836

Bravo AF: 0.835

Asia WGS AF: 0.791 AC: 2752 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	7.5
DANN	Benign	0.49

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: rs324582; hg19: chr7-136650607;