1-239773282-A-G

Position:

• chr1-239773282-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.-146-53970A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.635 in 151,990 control chromosomes in the GnomAD database, including 32,034 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 0.63 (32034 hom., cov: 31)
• Consequence: CHRM3 NM_001375978.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.425

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.741 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHRM3	NM_001375978.1	c.-146-53970A>G		intron_variant		ENST00000676153.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHRM3	ENST00000676153.1	c.-146-53970A>G		intron_variant			NM_001375978.1	P1

Frequencies

GnomAD3 genomes AF: 0.635 AC: 96469 AN: 151872 Hom.: 32043 Cov.: 31

Gnomad AFR AF: 0.456

Gnomad AMI AF: 0.754

Gnomad AMR AF: 0.689

Gnomad ASJ AF: 0.737

Gnomad EAS AF: 0.411

Gnomad SAS AF: 0.516

Gnomad FIN AF: 0.651

Gnomad MID AF: 0.720

Gnomad NFE AF: 0.746

Gnomad OTH AF: 0.689

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

GnomAD4 genome AF: 0.635 AC: 96476 AN: 151990 Hom.: 32034 Cov.: 31 AF XY: 0.628 AC XY: 46646 AN XY: 74312

Gnomad4 AFR AF: 0.455

Gnomad4 AMR AF: 0.689

Gnomad4 ASJ AF: 0.737

Gnomad4 EAS AF: 0.411

Gnomad4 SAS AF: 0.517

Gnomad4 FIN AF: 0.651

Gnomad4 NFE AF: 0.746

Gnomad4 OTH AF: 0.686

Alfa AF: 0.731 Hom.: 42679

Bravo AF: 0.631

Asia WGS AF: 0.475 AC: 1653 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.43
DANN	Benign	0.23

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: rs481036; hg19: chr1-239936582;