rs1594513

Variant names:

• chr1-239848453-A-C
• rs1594513
• NM_001375978.1:c.-20+21075A>C

Variant summary

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

The NM_001375978.1(CHRM3):​c.-20+21075A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.189 in 152,014 control chromosomes in the GnomAD database, including 3,367 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 0.19 (3367 hom., cov: 32)
• Consequence: CHRM3 NM_001375978.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.473
• Publications: 6 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.246 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHRM3	NM_001375978.1	c.-20+21075A>C		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.-20+21075A>C		intron_variant	Intron 6 of 6		NM_001375978.1	ENSP00000502667.1

Frequencies

GnomAD3 genomes AF: 0.189 AC: 28668 AN: 151896 Hom.: 3365 Cov.: 32

Gnomad AFR AF: 0.0494

Gnomad AMI AF: 0.271

Gnomad AMR AF: 0.245

Gnomad ASJ AF: 0.281

Gnomad EAS AF: 0.124

Gnomad SAS AF: 0.137

Gnomad FIN AF: 0.276

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.249

Gnomad OTH AF: 0.214

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

GnomAD4 genome AF: 0.189 AC: 28662 AN: 152014 Hom.: 3367 Cov.: 32 AF XY: 0.189 AC XY: 14028 AN XY: 74320

African (AFR) AF: 0.0493 AC: 2045 AN: 41502

American (AMR) AF: 0.245 AC: 3732 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.281 AC: 976 AN: 3468

East Asian (EAS) AF: 0.124 AC: 642 AN: 5180

South Asian (SAS) AF: 0.138 AC: 664 AN: 4812

European-Finnish (FIN) AF: 0.276 AC: 2921 AN: 10570

Middle Eastern (MID) AF: 0.238 AC: 70 AN: 294

European-Non Finnish (NFE) AF: 0.249 AC: 16915 AN: 67934

Other (OTH) AF: 0.214 AC: 451 AN: 2112

Alfa AF: 0.233 Hom.: 5914

Bravo AF: 0.181

Asia WGS AF: 0.125 AC: 434 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.7
DANN	Benign	0.45
PhyloP100		0.47
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: rs1594513; hg19: chr1-240011753;