rs8191992

Variant names:

• chr7-137016561-T-A
• rs8191992
• NM_001006630.2:c.*295T>A

Variant summary

Our verdict is Benign. The variant received -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:3
• Conservation: PhyloP100: -0.0930
• Publications: 31 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 -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 VariationId 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 rank	MANE	Protein	UniProt
CHRM2	NM_001006630.2	c.*295T>A		3_prime_UTR_variant	Exon 4 of 4	ENST00000680005.1	NP_001006631.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHRM2	ENST00000680005.1	c.*295T>A		3_prime_UTR_variant	Exon 4 of 4		NM_001006630.2	ENSP00000505686.1

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

African (AFR) AF: 0.773 AC: 5015 AN: 6484

American (AMR) AF: 0.373 AC: 3324 AN: 8904

Ashkenazi Jewish (ASJ) AF: 0.571 AC: 3479 AN: 6098

East Asian (EAS) AF: 0.112 AC: 1332 AN: 11888

South Asian (SAS) AF: 0.252 AC: 6318 AN: 25116

European-Finnish (FIN) AF: 0.584 AC: 13142 AN: 22488

Middle Eastern (MID) AF: 0.551 AC: 463 AN: 840

European-Non Finnish (NFE) AF: 0.533 AC: 64452 AN: 120942

Other (OTH) AF: 0.507 AC: 5906 AN: 11654

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

African (AFR) AF: 0.782 AC: 32447 AN: 41468

American (AMR) AF: 0.427 AC: 6499 AN: 15224

Ashkenazi Jewish (ASJ) AF: 0.562 AC: 1950 AN: 3468

East Asian (EAS) AF: 0.0990 AC: 507 AN: 5120

South Asian (SAS) AF: 0.251 AC: 1211 AN: 4818

European-Finnish (FIN) AF: 0.589 AC: 6224 AN: 10574

Middle Eastern (MID) AF: 0.585 AC: 172 AN: 294

European-Non Finnish (NFE) AF: 0.537 AC: 36466 AN: 67860

Other (OTH) AF: 0.557 AC: 1176 AN: 2110

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:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Jun 18, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Dilated Cardiomyopathy, Dominant Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	3.8
DANN	Benign	0.72
PhyloP100		-0.093
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: rs8191992; hg19: chr7-136701308; COSMIC: COSV57773628; COSMIC: COSV57773628;