1-239907303-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.28

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]

ACMG classification

Verdict is Benign. Variant got -14 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_single_submitter, 1 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	c.-19-130T>C		intron_variant		ENST00000676153.1

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.234 AC: 35639 AN: 151994 Hom.: 4323 Cov.: 32

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

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.: 32 AF XY: 0.234 AC XY: 17399 AN XY: 74368

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:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

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

Other links and lift over

dbSNP: rs3738435; hg19: chr1-240070603; COSMIC: COSV55086380;