7-136947256-G-C

Variant names:

• chr7-136947256-G-C
• rs1424543
• NM_001006630.2:c.-124-44931G>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.-124-44931G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.246 in 151,804 control chromosomes in the GnomAD database, including 5,685 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 0.25 (5685 hom., cov: 32)
• Consequence: CHRM2 NM_001006630.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.225
• Publications: 3 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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.342 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHRM2	NM_001006630.2	c.-124-44931G>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.-124-44931G>C		intron_variant	Intron 2 of 3		NM_001006630.2	ENSP00000505686.1

Frequencies

GnomAD3 genomes AF: 0.246 AC: 37293 AN: 151688 Hom.: 5687 Cov.: 32

Gnomad AFR AF: 0.0961

Gnomad AMI AF: 0.299

Gnomad AMR AF: 0.241

Gnomad ASJ AF: 0.316

Gnomad EAS AF: 0.0203

Gnomad SAS AF: 0.135

Gnomad FIN AF: 0.318

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.346

Gnomad OTH AF: 0.285

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

GnomAD4 genome AF: 0.246 AC: 37282 AN: 151804 Hom.: 5685 Cov.: 32 AF XY: 0.241 AC XY: 17880 AN XY: 74190

African (AFR) AF: 0.0958 AC: 3965 AN: 41402

American (AMR) AF: 0.241 AC: 3661 AN: 15216

Ashkenazi Jewish (ASJ) AF: 0.316 AC: 1096 AN: 3468

East Asian (EAS) AF: 0.0203 AC: 105 AN: 5170

South Asian (SAS) AF: 0.135 AC: 649 AN: 4806

European-Finnish (FIN) AF: 0.318 AC: 3347 AN: 10538

Middle Eastern (MID) AF: 0.337 AC: 99 AN: 294

European-Non Finnish (NFE) AF: 0.346 AC: 23494 AN: 67890

Other (OTH) AF: 0.281 AC: 593 AN: 2108

Alfa AF: 0.165 Hom.: 373

Bravo AF: 0.235

Asia WGS AF: 0.0910 AC: 316 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.85
DANN	Benign	0.69
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: rs1424543; hg19: chr7-136632003;