chr1-239806797-A-G

Position:

• chr1-239806797-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001375978.1(CHRM3):​c.-146-20455A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.293 in 152,174 control chromosomes in the GnomAD database, including 8,034 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.29 (8034 hom., cov: 33)
• Consequence: CHRM3 NM_001375978.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0490

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.505 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHRM3	NM_001375978.1	c.-146-20455A>G		intron_variant		ENST00000676153.1	NP_001362907.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHRM3	ENST00000676153.1	c.-146-20455A>G		intron_variant			NM_001375978.1	ENSP00000502667.1

Frequencies

GnomAD3 genomes AF: 0.293 AC: 44603 AN: 152056 Hom.: 8022 Cov.: 33

Gnomad AFR AF: 0.511

Gnomad AMI AF: 0.113

Gnomad AMR AF: 0.256

Gnomad ASJ AF: 0.225

Gnomad EAS AF: 0.311

Gnomad SAS AF: 0.197

Gnomad FIN AF: 0.183

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.199

Gnomad OTH AF: 0.273

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.293 AC: 44639 AN: 152174 Hom.: 8034 Cov.: 33 AF XY: 0.289 AC XY: 21498 AN XY: 74394

Gnomad4 AFR AF: 0.511

Gnomad4 AMR AF: 0.255

Gnomad4 ASJ AF: 0.225

Gnomad4 EAS AF: 0.311

Gnomad4 SAS AF: 0.197

Gnomad4 FIN AF: 0.183

Gnomad4 NFE AF: 0.199

Gnomad4 OTH AF: 0.269

Alfa AF: 0.209 Hom.: 7338

Bravo AF: 0.307

Asia WGS AF: 0.298 AC: 1038 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	6.2
DANN	Benign	0.68

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs12059546; hg19: chr1-239970097;