rs8191993

Positions:

• chr7-137016816-G-C
• chr7-137016816-G-T

Variant summary

Our verdict is Benign. Variant got -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

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHRM2	NM_001006630.2	c.*550G>C		3_prime_UTR_variant	4/4	ENST00000680005.1
LOC349160	NR_046103.1	n.341+15978C>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHRM2	ENST00000680005.1	c.*550G>C		3_prime_UTR_variant	4/4		NM_001006630.2	P1
	ENST00000586239.5	n.273+15978C>G		intron_variant, non_coding_transcript_variant		5

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

Gnomad4 AFR exome AF: 1.00

Gnomad4 AMR exome AF: 0.702

Gnomad4 EAS exome AF: 0.286

Gnomad4 SAS exome AF: 0.235

Gnomad4 FIN exome AF: 0.771

Gnomad4 NFE exome AF: 0.625

Gnomad4 OTH exome AF: 0.591

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

Gnomad4 AFR AF: 0.805

Gnomad4 AMR AF: 0.687

Gnomad4 ASJ AF: 0.724

Gnomad4 EAS AF: 0.452

Gnomad4 SAS AF: 0.505

Gnomad4 FIN AF: 0.758

Gnomad4 NFE AF: 0.665

Gnomad4 OTH AF: 0.691

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.9
DANN	Benign	0.65

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

Publications

LitVar

Other links and lift over

dbSNP: rs8191993; hg19: chr7-136701563; COSMIC: COSV57772641; COSMIC: COSV57772641;