rs420817

Variant names:

• chr7-137002656-C-T
• rs420817
• NM_001006630.2:c.-47+10392C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001006630.2(CHRM2):​c.-47+10392C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.458 in 151,630 control chromosomes in the GnomAD database, including 16,681 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 0.46 (16681 hom., cov: 32)
• Consequence: CHRM2 NM_001006630.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.261
• Publications: 5 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.486 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHRM2	NM_001006630.2	c.-47+10392C>T		intron_variant	Intron 3 of 3	ENST00000680005.1	NP_001006631.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHRM2	ENST00000680005.1	c.-47+10392C>T		intron_variant	Intron 3 of 3		NM_001006630.2	ENSP00000505686.1

Frequencies

GnomAD3 genomes AF: 0.458 AC: 69450 AN: 151510 Hom.: 16660 Cov.: 32

Gnomad AFR AF: 0.487

Gnomad AMI AF: 0.473

Gnomad AMR AF: 0.371

Gnomad ASJ AF: 0.528

Gnomad EAS AF: 0.0451

Gnomad SAS AF: 0.218

Gnomad FIN AF: 0.556

Gnomad MID AF: 0.525

Gnomad NFE AF: 0.490

Gnomad OTH AF: 0.471

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

GnomAD4 genome AF: 0.458 AC: 69511 AN: 151630 Hom.: 16681 Cov.: 32 AF XY: 0.454 AC XY: 33611 AN XY: 74072

African (AFR) AF: 0.487 AC: 20153 AN: 41358

American (AMR) AF: 0.370 AC: 5635 AN: 15224

Ashkenazi Jewish (ASJ) AF: 0.528 AC: 1832 AN: 3468

East Asian (EAS) AF: 0.0454 AC: 235 AN: 5174

South Asian (SAS) AF: 0.218 AC: 1049 AN: 4822

European-Finnish (FIN) AF: 0.556 AC: 5821 AN: 10476

Middle Eastern (MID) AF: 0.534 AC: 157 AN: 294

European-Non Finnish (NFE) AF: 0.490 AC: 33226 AN: 67816

Other (OTH) AF: 0.466 AC: 975 AN: 2094

Alfa AF: 0.479 Hom.: 28233

Bravo AF: 0.449

Asia WGS AF: 0.178 AC: 620 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.19
DANN	Benign	0.41
PhyloP100		0.26
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: rs420817; hg19: chr7-136687403;