NM_001006630.2:c.*550G>C

Variant names:

• chr7-137016816-G-C
• rs8191993
• NM_001006630.2:c.*550G>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.*550G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.707 in 167,350 control chromosomes in the GnomAD database, including 42,470 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 0.70 (37955 hom., cov: 32)
  • Exomes 𝑓: 0.76 (4515 hom.)
• Consequence: CHRM2 NM_001006630.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.497
• Publications: 9 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.797 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.*550G>C		3_prime_UTR	Exon 4 of 4	NP_001006631.1	P08172
	CHRM2	NM_000739.3		c.*550G>C		3_prime_UTR	Exon 4 of 4	NP_000730.1	P08172
	CHRM2	NM_001006626.3		c.*550G>C		3_prime_UTR	Exon 5 of 5	NP_001006627.1	A4D1Q0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHRM2	ENST00000680005.1	MANE Select	c.*550G>C		3_prime_UTR	Exon 4 of 4	ENSP00000505686.1	P08172
	CHRM2	ENST00000401861.1	TSL:1	c.*550G>C		3_prime_UTR	Exon 5 of 5	ENSP00000384401.1	P08172
	CHRM2	ENST00000445907.6	TSL:1	c.*550G>C		3_prime_UTR	Exon 3 of 3	ENSP00000399745.2	P08172

Frequencies

GnomAD3 genomes AF: 0.701 AC: 106381 AN: 151708 Hom.: 37914 Cov.: 32

Gnomad AFR AF: 0.805

Gnomad AMI AF: 0.616

Gnomad AMR AF: 0.687

Gnomad ASJ AF: 0.724

Gnomad EAS AF: 0.452

Gnomad SAS AF: 0.505

Gnomad FIN AF: 0.758

Gnomad MID AF: 0.694

Gnomad NFE AF: 0.665

Gnomad OTH AF: 0.698

GnomAD4 exome AF: 0.763 AC: 11841 AN: 15524 Hom.: 4515 Cov.: 0 AF XY: 0.763 AC XY: 5644 AN XY: 7394

African (AFR) AF: 1.00 AC: 4 AN: 4

American (AMR) AF: 0.702 AC: 59 AN: 84

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.286 AC: 4 AN: 14

South Asian (SAS) AF: 0.235 AC: 8 AN: 34

European-Finnish (FIN) AF: 0.771 AC: 11341 AN: 14700

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2

European-Non Finnish (NFE) AF: 0.625 AC: 360 AN: 576

Other (OTH) AF: 0.591 AC: 65 AN: 110

GnomAD4 genome AF: 0.701 AC: 106471 AN: 151826 Hom.: 37955 Cov.: 32 AF XY: 0.701 AC XY: 51995 AN XY: 74184

African (AFR) AF: 0.805 AC: 33356 AN: 41452

American (AMR) AF: 0.687 AC: 10448 AN: 15208

Ashkenazi Jewish (ASJ) AF: 0.724 AC: 2512 AN: 3468

East Asian (EAS) AF: 0.452 AC: 2308 AN: 5104

South Asian (SAS) AF: 0.505 AC: 2435 AN: 4820

European-Finnish (FIN) AF: 0.758 AC: 8037 AN: 10596

Middle Eastern (MID) AF: 0.688 AC: 201 AN: 292

European-Non Finnish (NFE) AF: 0.665 AC: 45151 AN: 67860

Other (OTH) AF: 0.691 AC: 1461 AN: 2114

Alfa AF: 0.606 Hom.: 1945

Bravo AF: 0.703

Asia WGS AF: 0.513 AC: 1786 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.9
DANN	Benign	0.65
PhyloP100		0.50
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: rs8191993; hg19: chr7-136701563; COSMIC: COSV57772641; COSMIC: COSV57772641;