Variant 1-239907303-T-C 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_001375978.1(CHRM3):c.-19-130T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.221 in 640,720 control chromosomes in the GnomAD database, including 16,321 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.23 ( 4334 hom., cov: 32)

Exomes 𝑓: 0.22 ( 11987 hom. )

Consequence

CHRM3
NM_001375978.1 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.28

Variant links:

Genes affected

CHRM3 (HGNC:1952): (cholinergic receptor muscarinic 3) 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 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 3 controls smooth muscle contraction and its stimulation causes secretion of glandular tissue. Alternative promoter use and alternative splicing results in multiple transcript variants that have different tissue specificities. [provided by RefSeq, Dec 2016]

CHRM3 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=-0.85).

BP6

Variant 1-239907303-T-C is Benign according to our data. Variant chr1-239907303-T-C is described in ClinVar as [Benign]. Clinvar id is 1253741.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.365 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHRM3	NM_001375978.1 linkuse as main transcript	c.-19-130T>C		intron_variant		ENST00000676153.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHRM3	ENST00000676153.1 linkuse as main transcript	c.-19-130T>C		intron_variant			NM_001375978.1	P1

Frequencies

GnomAD3 genomes

AF:

0.234

AC:

35639

AN:

151994

Hom.:

4323

Cov.:

show subpopulations

Gnomad AFR

AF:

0.273

Gnomad AMI

AF:

0.172

Gnomad AMR

AF:

0.254

Gnomad ASJ

AF:

0.224

Gnomad EAS

AF:

0.379

Gnomad SAS

AF:

0.212

Gnomad FIN

AF:

0.220

Gnomad MID

AF:

0.250

Gnomad NFE

AF:

0.200

Gnomad OTH

AF:

0.251

GnomAD4 exome

AF:

0.216

AC:

105780

AN:

488608

Hom.:

11987

AF XY:

0.215

AC XY:

54983

AN XY:

255618

show subpopulations

Gnomad4 AFR exome

AF:

0.271

Gnomad4 AMR exome

AF:

0.276

Gnomad4 ASJ exome

AF:

0.222

Gnomad4 EAS exome

AF:

0.318

Gnomad4 SAS exome

AF:

0.199

Gnomad4 FIN exome

AF:

0.223

Gnomad4 NFE exome

AF:

0.200

Gnomad4 OTH exome

AF:

0.229

GnomAD4 genome

AF:

0.235

AC:

35683

AN:

152112

Hom.:

4334

Cov.:

AF XY:

0.234

AC XY:

17399

AN XY:

74368

show subpopulations

Gnomad4 AFR

AF:

0.273

Gnomad4 AMR

AF:

0.254

Gnomad4 ASJ

AF:

0.224

Gnomad4 EAS

AF:

0.379

Gnomad4 SAS

AF:

0.212

Gnomad4 FIN

AF:

0.220

Gnomad4 NFE

AF:

0.201

Gnomad4 OTH

AF:

0.254

Alfa

AF:

0.226

Hom.:

1134

Bravo

AF:

0.242

Asia WGS

AF:

0.299

AC:

1038

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	This variant is associated with the following publications: (PMID: 17130513) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.79

DANN

Benign

0.24

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