rs481036

Variant names:

• chr1-239773282-A-G
• rs481036
• NM_001375978.1:c.-146-53970A>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.-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
• Publications: 3 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=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.741 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.-146-53970A>G		intron	N/A	NP_001362907.1	P20309
	CHRM3	NM_000740.4		c.-146-53970A>G		intron	N/A	NP_000731.1	P20309
	CHRM3	NM_001347716.2		c.-375-53571A>G		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.-146-53970A>G		intron	N/A	ENSP00000502667.1	P20309
	CHRM3	ENST00000255380.8	TSL:1	c.-146-53970A>G		intron	N/A	ENSP00000255380.4	P20309
	CHRM3	ENST00000615928.5	TSL:5	c.-146-53970A>G		intron	N/A	ENSP00000482377.1	P20309

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

African (AFR) AF: 0.455 AC: 18876 AN: 41462

American (AMR) AF: 0.689 AC: 10513 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.737 AC: 2557 AN: 3470

East Asian (EAS) AF: 0.411 AC: 2127 AN: 5170

South Asian (SAS) AF: 0.517 AC: 2485 AN: 4808

European-Finnish (FIN) AF: 0.651 AC: 6876 AN: 10558

Middle Eastern (MID) AF: 0.702 AC: 205 AN: 292

European-Non Finnish (NFE) AF: 0.746 AC: 50702 AN: 67954

Other (OTH) AF: 0.686 AC: 1447 AN: 2110

Alfa AF: 0.722 Hom.: 61793

Bravo AF: 0.631

Asia WGS AF: 0.475 AC: 1653 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.43
DANN	Benign	0.23
PhyloP100		-0.42
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: rs481036; hg19: chr1-239936582;