NM_001006630.2:c.-124-28090T>C

Variant names:

• chr7-136964097-T-C
• rs324580
• NM_001006630.2:c.-124-28090T>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.-124-28090T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.876 in 152,142 control chromosomes in the GnomAD database, including 58,935 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 (58935 hom., cov: 31)
• Consequence: CHRM2 NM_001006630.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.141
• Publications: 2 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=-0.93).
• 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.-124-28090T>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.-124-28090T>C		intron_variant	Intron 2 of 3		NM_001006630.2	ENSP00000505686.1

Frequencies

GnomAD3 genomes AF: 0.876 AC: 133187 AN: 152024 Hom.: 58916 Cov.: 31

Gnomad AFR AF: 0.818

Gnomad AMI AF: 0.943

Gnomad AMR AF: 0.752

Gnomad ASJ AF: 0.975

Gnomad EAS AF: 0.688

Gnomad SAS AF: 0.828

Gnomad FIN AF: 0.968

Gnomad MID AF: 0.968

Gnomad NFE AF: 0.936

Gnomad OTH AF: 0.879

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

GnomAD4 genome AF: 0.876 AC: 133251 AN: 152142 Hom.: 58935 Cov.: 31 AF XY: 0.876 AC XY: 65146 AN XY: 74392

African (AFR) AF: 0.818 AC: 33937 AN: 41486

American (AMR) AF: 0.750 AC: 11459 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.975 AC: 3383 AN: 3470

East Asian (EAS) AF: 0.687 AC: 3549 AN: 5166

South Asian (SAS) AF: 0.829 AC: 3987 AN: 4810

European-Finnish (FIN) AF: 0.968 AC: 10261 AN: 10604

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

European-Non Finnish (NFE) AF: 0.936 AC: 63675 AN: 68018

Other (OTH) AF: 0.879 AC: 1858 AN: 2114

Alfa AF: 0.905 Hom.: 45850

Bravo AF: 0.854

Asia WGS AF: 0.779 AC: 2712 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	5.7
DANN	Benign	0.33
PhyloP100		0.14
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: rs324580; hg19: chr7-136648844;