Variant rs8191992 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.0930

Variant links:

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]

CHRM2 links:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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	Protein	UniProt
CHRM2	NM_001006630.2 linkuse as main transcript	c.*295T>A		3_prime_UTR_variant	4/4	ENST00000680005.1	NP_001006631.1
LOC349160	NR_046103.1 linkuse as main transcript	n.341+16233A>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHRM2	ENST00000680005.1 linkuse as main transcript	c.*295T>A		3_prime_UTR_variant	4/4		NM_001006630.2	ENSP00000505686	P1
	ENST00000586239.5 linkuse as main transcript	n.273+16233A>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

AF:

0.574

AC:

87074

AN:

151728

Hom.:

27037

Cov.:

show subpopulations

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.:

AF XY:

0.464

AC XY:

51907

AN XY:

111964

show subpopulations

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.:

AF XY:

0.567

AC XY:

42086

AN XY:

74230

show subpopulations

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:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 18, 2018	This variant is associated with the following publications: (PMID: 12116189) -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Dilated Cardiomyopathy, Dominant

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 04, 2020

- -

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over