7-137008005-T-C

Variant names:

• chr7-137008005-T-C
• rs324647
• NM_001006630.2:c.-46-6815T>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.-46-6815T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.144 in 152,086 control chromosomes in the GnomAD database, including 1,914 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 0.14 (1914 hom., cov: 32)
• Consequence: CHRM2 NM_001006630.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.356
• 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=-0.79).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.218 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHRM2	NM_001006630.2	MANE Select	c.-46-6815T>C		intron	N/A	NP_001006631.1	P08172
	CHRM2	NM_000739.3		c.-46-6815T>C		intron	N/A	NP_000730.1	P08172
	CHRM2	NM_001006626.3		c.-46-6815T>C		intron	N/A	NP_001006627.1	A4D1Q0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHRM2	ENST00000680005.1	MANE Select	c.-46-6815T>C		intron	N/A	ENSP00000505686.1	P08172
	CHRM2	ENST00000320658.9	TSL:1	c.-46-6815T>C		intron	N/A	ENSP00000319984.5	P08172
	CHRM2	ENST00000401861.1	TSL:1	c.-46-6815T>C		intron	N/A	ENSP00000384401.1	P08172

Frequencies

GnomAD3 genomes AF: 0.144 AC: 21912 AN: 151968 Hom.: 1910 Cov.: 32

Gnomad AFR AF: 0.222

Gnomad AMI AF: 0.154

Gnomad AMR AF: 0.0951

Gnomad ASJ AF: 0.172

Gnomad EAS AF: 0.0395

Gnomad SAS AF: 0.0573

Gnomad FIN AF: 0.190

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.114

Gnomad OTH AF: 0.140

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

GnomAD4 genome AF: 0.144 AC: 21923 AN: 152086 Hom.: 1914 Cov.: 32 AF XY: 0.145 AC XY: 10808 AN XY: 74326

African (AFR) AF: 0.222 AC: 9201 AN: 41484

American (AMR) AF: 0.0948 AC: 1448 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.172 AC: 595 AN: 3468

East Asian (EAS) AF: 0.0396 AC: 204 AN: 5158

South Asian (SAS) AF: 0.0578 AC: 279 AN: 4830

European-Finnish (FIN) AF: 0.190 AC: 2010 AN: 10580

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.114 AC: 7716 AN: 67974

Other (OTH) AF: 0.139 AC: 295 AN: 2116

Alfa AF: 0.126 Hom.: 3147

Bravo AF: 0.141

Asia WGS AF: 0.0810 AC: 280 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	3.7
DANN	Benign	0.88
PhyloP100		0.36
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: rs324647; hg19: chr7-136692752;