rs536477

Variant names:

• chr1-239882608-A-G
• rs536477
• NM_001375978.1:c.-19-24825A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001375978.1(CHRM3):​c.-19-24825A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.5 in 152,100 control chromosomes in the GnomAD database, including 20,573 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 0.50 (20573 hom., cov: 33)
• Consequence: CHRM3 NM_001375978.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.118
• Publications: 9 publications found

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 Gene-Disease associations (from GenCC):

• prune belly syndrome

  Inheritance: AR, AD Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.624 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHRM3	NM_001375978.1	c.-19-24825A>G		intron_variant	Intron 6 of 6	ENST00000676153.1	NP_001362907.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHRM3	ENST00000676153.1	c.-19-24825A>G		intron_variant	Intron 6 of 6		NM_001375978.1	ENSP00000502667.1

Frequencies

GnomAD3 genomes AF: 0.500 AC: 75994 AN: 151982 Hom.: 20575 Cov.: 33

Gnomad AFR AF: 0.265

Gnomad AMI AF: 0.483

Gnomad AMR AF: 0.546

Gnomad ASJ AF: 0.582

Gnomad EAS AF: 0.642

Gnomad SAS AF: 0.577

Gnomad FIN AF: 0.630

Gnomad MID AF: 0.639

Gnomad NFE AF: 0.591

Gnomad OTH AF: 0.518

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

GnomAD4 genome AF: 0.500 AC: 75990 AN: 152100 Hom.: 20573 Cov.: 33 AF XY: 0.504 AC XY: 37475 AN XY: 74348

African (AFR) AF: 0.264 AC: 10974 AN: 41516

American (AMR) AF: 0.546 AC: 8350 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.582 AC: 2021 AN: 3470

East Asian (EAS) AF: 0.642 AC: 3308 AN: 5152

South Asian (SAS) AF: 0.576 AC: 2774 AN: 4812

European-Finnish (FIN) AF: 0.630 AC: 6660 AN: 10568

Middle Eastern (MID) AF: 0.626 AC: 184 AN: 294

European-Non Finnish (NFE) AF: 0.591 AC: 40197 AN: 67988

Other (OTH) AF: 0.513 AC: 1083 AN: 2112

Alfa AF: 0.567 Hom.: 110712

Bravo AF: 0.489

Asia WGS AF: 0.541 AC: 1884 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.1
DANN	Benign	0.82
PhyloP100		0.12
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs536477; hg19: chr1-240045908;