rs8191992

chr7-137016561-T-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001006630.2(CHRM2):c.*295T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.52 in 366,260 control chromosomes in the GnomAD database, including 54,594 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.57 (27081 hom., cov: 32)
  • Exomes 𝑓: 0.48 (27513 hom.)
• Consequence: CHRM2 NM_001006630.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0930

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 7-137016561-T-A is Benign according to our data. Variant chr7-137016561-T-A is described in ClinVar as [Benign]. Clinvar id is 703788.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.775 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHRM2	NM_001006630.2	c.*295T>A		3_prime_UTR_variant	4/4	ENST00000680005.1
LOC349160	NR_046103.1	n.341+16233A>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHRM2	ENST00000680005.1	c.*295T>A		3_prime_UTR_variant	4/4		NM_001006630.2	P1
	ENST00000586239.5	n.273+16233A>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.574 AC: 87074 AN: 151728 Hom.: 27037 Cov.: 32

Gnomad AFR AF: 0.782

Gnomad AMI AF: 0.559

Gnomad AMR AF: 0.428

Gnomad ASJ AF: 0.562

Gnomad EAS AF: 0.0990

Gnomad SAS AF: 0.252

Gnomad FIN AF: 0.589

Gnomad MID AF: 0.582

Gnomad NFE AF: 0.537

Gnomad OTH AF: 0.563

GnomAD4 exome AF: 0.482 AC: 103431 AN: 214414 Hom.: 27513 Cov.: 0 AF XY: 0.464 AC XY: 51907 AN XY: 111964

Gnomad4 AFR exome AF: 0.773

Gnomad4 AMR exome AF: 0.373

Gnomad4 ASJ exome AF: 0.571

Gnomad4 EAS exome AF: 0.112

Gnomad4 SAS exome AF: 0.252

Gnomad4 FIN exome AF: 0.584

Gnomad4 NFE exome AF: 0.533

Gnomad4 OTH exome AF: 0.507

GnomAD4 genome AF: 0.574 AC: 87161 AN: 151846 Hom.: 27081 Cov.: 32 AF XY: 0.567 AC XY: 42086 AN XY: 74230

Gnomad4 AFR AF: 0.782

Gnomad4 AMR AF: 0.427

Gnomad4 ASJ AF: 0.562

Gnomad4 EAS AF: 0.0990

Gnomad4 SAS AF: 0.251

Gnomad4 FIN AF: 0.589

Gnomad4 NFE AF: 0.537

Gnomad4 OTH AF: 0.557

Alfa AF: 0.566 Hom.: 3146

Bravo AF: 0.573

Asia WGS AF: 0.242 AC: 843 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Dilated Cardiomyopathy, Dominant Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 04, 2020

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 18, 2018

This variant is associated with the following publications: (PMID: 12116189) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
Cadd	Benign	3.8
Dann	Benign	0.72

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: rs8191992; hg19: chr7-136701308; COSMIC: COSV57773628; COSMIC: COSV57773628;