rs1578180

Variant names:

• chr1-239819338-G-A
• rs1578180
• NM_001375978.1:c.-146-7914G>A

Variant summary

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

The NM_001375978.1(CHRM3):​c.-146-7914G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.196 in 152,050 control chromosomes in the GnomAD database, including 2,935 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 0.20 (2935 hom., cov: 32)
• Consequence: CHRM3 NM_001375978.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0520
• Publications: 5 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: AD, AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.208 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001375978.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHRM3	NM_001375978.1	MANE Select	c.-146-7914G>A		intron	N/A	NP_001362907.1	P20309
	CHRM3	NM_000740.4		c.-146-7914G>A		intron	N/A	NP_000731.1	P20309
	CHRM3	NM_001347716.2		c.-375-7515G>A		intron	N/A	NP_001334645.1	P20309

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHRM3	ENST00000676153.1	MANE Select	c.-146-7914G>A		intron	N/A	ENSP00000502667.1	P20309
	CHRM3	ENST00000255380.8	TSL:1	c.-146-7914G>A		intron	N/A	ENSP00000255380.4	P20309
	CHRM3	ENST00000615928.5	TSL:5	c.-146-7914G>A		intron	N/A	ENSP00000482377.1	P20309

Frequencies

GnomAD3 genomes AF: 0.196 AC: 29741 AN: 151932 Hom.: 2937 Cov.: 32

Gnomad AFR AF: 0.210

Gnomad AMI AF: 0.105

Gnomad AMR AF: 0.212

Gnomad ASJ AF: 0.214

Gnomad EAS AF: 0.178

Gnomad SAS AF: 0.219

Gnomad FIN AF: 0.171

Gnomad MID AF: 0.188

Gnomad NFE AF: 0.187

Gnomad OTH AF: 0.212

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

GnomAD4 genome AF: 0.196 AC: 29752 AN: 152050 Hom.: 2935 Cov.: 32 AF XY: 0.195 AC XY: 14491 AN XY: 74300

African (AFR) AF: 0.210 AC: 8725 AN: 41496

American (AMR) AF: 0.211 AC: 3230 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.214 AC: 743 AN: 3470

East Asian (EAS) AF: 0.178 AC: 914 AN: 5138

South Asian (SAS) AF: 0.219 AC: 1053 AN: 4806

European-Finnish (FIN) AF: 0.171 AC: 1811 AN: 10562

Middle Eastern (MID) AF: 0.185 AC: 54 AN: 292

European-Non Finnish (NFE) AF: 0.187 AC: 12686 AN: 67986

Other (OTH) AF: 0.209 AC: 440 AN: 2108

Alfa AF: 0.191 Hom.: 12451

Bravo AF: 0.197

Asia WGS AF: 0.210 AC: 731 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.97
DANN	Benign	0.43
PhyloP100		-0.052
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: rs1578180; hg19: chr1-239982638;