rs1424569

Positions:

• chr7-136884669-T-C

Variant summary

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

The NM_001006630.2(CHRM2):​c.-125+15251T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.5 in 151,886 control chromosomes in the GnomAD database, including 19,598 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 0.50 (19598 hom., cov: 31)
• Consequence: CHRM2 NM_001006630.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.912

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.543 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHRM2	NM_001006630.2	c.-125+15251T>C		intron_variant		ENST00000680005.1	NP_001006631.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHRM2	ENST00000680005.1	c.-125+15251T>C		intron_variant			NM_001006630.2	ENSP00000505686.1

Frequencies

GnomAD3 genomes AF: 0.500 AC: 75863 AN: 151768 Hom.: 19585 Cov.: 31

Gnomad AFR AF: 0.549

Gnomad AMI AF: 0.447

Gnomad AMR AF: 0.417

Gnomad ASJ AF: 0.536

Gnomad EAS AF: 0.128

Gnomad SAS AF: 0.305

Gnomad FIN AF: 0.471

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.535

Gnomad OTH AF: 0.488

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

GnomAD4 genome AF: 0.500 AC: 75909 AN: 151886 Hom.: 19598 Cov.: 31 AF XY: 0.487 AC XY: 36128 AN XY: 74252

Gnomad4 AFR AF: 0.549

Gnomad4 AMR AF: 0.416

Gnomad4 ASJ AF: 0.536

Gnomad4 EAS AF: 0.127

Gnomad4 SAS AF: 0.308

Gnomad4 FIN AF: 0.471

Gnomad4 NFE AF: 0.535

Gnomad4 OTH AF: 0.484

Alfa AF: 0.520 Hom.: 27630

Bravo AF: 0.499

Asia WGS AF: 0.247 AC: 859 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.89
DANN	Benign	0.47

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: rs1424569; hg19: chr7-136569416;