NM_001006630.2:c.-124-16596T>C

Variant names:

• chr7-136975591-T-C
• rs324612
• NM_001006630.2:c.-124-16596T>C

Variant summary

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

The NM_001006630.2(CHRM2):​c.-124-16596T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.884 in 152,302 control chromosomes in the GnomAD database, including 59,956 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 0.88 (59956 hom., cov: 33)
• Consequence: CHRM2 NM_001006630.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.232
• Publications: 1 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 = 0.93 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHRM2	NM_001006630.2	c.-124-16596T>C		intron_variant	Intron 2 of 3	ENST00000680005.1	NP_001006631.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHRM2	ENST00000680005.1	c.-124-16596T>C		intron_variant	Intron 2 of 3		NM_001006630.2	ENSP00000505686.1

Frequencies

GnomAD3 genomes AF: 0.884 AC: 134586 AN: 152184 Hom.: 59939 Cov.: 33

Gnomad AFR AF: 0.822

Gnomad AMI AF: 0.943

Gnomad AMR AF: 0.807

Gnomad ASJ AF: 0.975

Gnomad EAS AF: 0.715

Gnomad SAS AF: 0.844

Gnomad FIN AF: 0.968

Gnomad MID AF: 0.968

Gnomad NFE AF: 0.936

Gnomad OTH AF: 0.891

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

GnomAD4 genome AF: 0.884 AC: 134648 AN: 152302 Hom.: 59956 Cov.: 33 AF XY: 0.885 AC XY: 65904 AN XY: 74474

African (AFR) AF: 0.822 AC: 34152 AN: 41556

American (AMR) AF: 0.806 AC: 12324 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.975 AC: 3385 AN: 3472

East Asian (EAS) AF: 0.713 AC: 3698 AN: 5184

South Asian (SAS) AF: 0.844 AC: 4080 AN: 4832

European-Finnish (FIN) AF: 0.968 AC: 10283 AN: 10626

Middle Eastern (MID) AF: 0.966 AC: 284 AN: 294

European-Non Finnish (NFE) AF: 0.936 AC: 63701 AN: 68024

Other (OTH) AF: 0.891 AC: 1881 AN: 2112

Alfa AF: 0.911 Hom.: 7876

Bravo AF: 0.866

Asia WGS AF: 0.802 AC: 2787 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.0
DANN	Benign	0.59
PhyloP100		-0.23
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: rs324612; hg19: chr7-136660338;