7-136948957-T-C

Variant names:

• chr7-136948957-T-C
• rs1111418
• NM_001006630.2:c.-124-43230T>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.-124-43230T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.315 in 151,914 control chromosomes in the GnomAD database, including 7,944 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 0.31 (7944 hom., cov: 31)
• Consequence: CHRM2 NM_001006630.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.288
• Publications: 4 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.412 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001006630.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHRM2	NM_001006630.2	MANE Select	c.-124-43230T>C		intron	N/A	NP_001006631.1
	CHRM2	NM_000739.3		c.-124-43230T>C		intron	N/A	NP_000730.1
	CHRM2	NM_001006626.3		c.-202-2046T>C		intron	N/A	NP_001006627.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHRM2	ENST00000680005.1	MANE Select	c.-124-43230T>C		intron	N/A	ENSP00000505686.1
	CHRM2	ENST00000320658.9	TSL:1	c.-46-65863T>C		intron	N/A	ENSP00000319984.5
	CHRM2	ENST00000401861.1	TSL:1	c.-202-2046T>C		intron	N/A	ENSP00000384401.1

Frequencies

GnomAD3 genomes AF: 0.315 AC: 47747 AN: 151796 Hom.: 7930 Cov.: 31

Gnomad AFR AF: 0.405

Gnomad AMI AF: 0.242

Gnomad AMR AF: 0.264

Gnomad ASJ AF: 0.304

Gnomad EAS AF: 0.428

Gnomad SAS AF: 0.334

Gnomad FIN AF: 0.308

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.265

Gnomad OTH AF: 0.288

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

GnomAD4 genome AF: 0.315 AC: 47797 AN: 151914 Hom.: 7944 Cov.: 31 AF XY: 0.317 AC XY: 23522 AN XY: 74228

African (AFR) AF: 0.405 AC: 16783 AN: 41428

American (AMR) AF: 0.264 AC: 4026 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.304 AC: 1054 AN: 3470

East Asian (EAS) AF: 0.427 AC: 2189 AN: 5126

South Asian (SAS) AF: 0.335 AC: 1615 AN: 4814

European-Finnish (FIN) AF: 0.308 AC: 3253 AN: 10556

Middle Eastern (MID) AF: 0.221 AC: 65 AN: 294

European-Non Finnish (NFE) AF: 0.264 AC: 17969 AN: 67940

Other (OTH) AF: 0.296 AC: 622 AN: 2102

Alfa AF: 0.304 Hom.: 2648

Bravo AF: 0.314

Asia WGS AF: 0.389 AC: 1351 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.2
DANN	Benign	0.53
PhyloP100		0.29
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: rs1111418; hg19: chr7-136633704;