NM_001006630.2:c.-124-53287T>C

Variant names:

• chr7-136938900-T-C
• rs36210735
• NM_001006630.2:c.-124-53287T>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.-124-53287T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.59 (18006 hom., cov: 15)
• Consequence: CHRM2 NM_001006630.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.259
• 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=-0.77).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.737 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHRM2	NM_001006630.2	c.-124-53287T>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.-124-53287T>C		intron_variant	Intron 2 of 3		NM_001006630.2	ENSP00000505686.1

Frequencies

GnomAD3 genomes AF: 0.592 AC: 61084 AN: 103136 Hom.: 17978 Cov.: 15

Gnomad AFR AF: 0.745

Gnomad AMI AF: 0.546

Gnomad AMR AF: 0.521

Gnomad ASJ AF: 0.566

Gnomad EAS AF: 0.0574

Gnomad SAS AF: 0.303

Gnomad FIN AF: 0.607

Gnomad MID AF: 0.629

Gnomad NFE AF: 0.559

Gnomad OTH AF: 0.595

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

GnomAD4 genome AF: 0.592 AC: 61128 AN: 103186 Hom.: 18006 Cov.: 15 AF XY: 0.590 AC XY: 28408 AN XY: 48110

African (AFR) AF: 0.745 AC: 21620 AN: 29020

American (AMR) AF: 0.520 AC: 4402 AN: 8462

Ashkenazi Jewish (ASJ) AF: 0.566 AC: 1536 AN: 2716

East Asian (EAS) AF: 0.0563 AC: 144 AN: 2558

South Asian (SAS) AF: 0.302 AC: 720 AN: 2386

European-Finnish (FIN) AF: 0.607 AC: 2774 AN: 4572

Middle Eastern (MID) AF: 0.630 AC: 102 AN: 162

European-Non Finnish (NFE) AF: 0.559 AC: 28688 AN: 51332

Other (OTH) AF: 0.593 AC: 785 AN: 1324

Alfa AF: 0.551 Hom.: 1963

Bravo AF: 0.537

Asia WGS AF: 0.128 AC: 414 AN: 3212

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	2.1
DANN	Benign	0.43
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: rs36210735; hg19: chr7-136623647;