rs10495447

Variant names:

• chr1-239888040-G-A
• rs10495447
• NM_001375978.1:c.-19-19393G>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.-19-19393G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.252 in 151,986 control chromosomes in the GnomAD database, including 5,275 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 0.25 (5275 hom., cov: 32)
• Consequence: CHRM3 NM_001375978.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.457
• 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=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.333 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHRM3	NM_001375978.1	c.-19-19393G>A		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.-19-19393G>A		intron_variant	Intron 6 of 6		NM_001375978.1	ENSP00000502667.1

Frequencies

GnomAD3 genomes AF: 0.252 AC: 38234 AN: 151864 Hom.: 5265 Cov.: 32

Gnomad AFR AF: 0.125

Gnomad AMI AF: 0.302

Gnomad AMR AF: 0.311

Gnomad ASJ AF: 0.278

Gnomad EAS AF: 0.289

Gnomad SAS AF: 0.346

Gnomad FIN AF: 0.287

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.298

Gnomad OTH AF: 0.273

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

GnomAD4 genome AF: 0.252 AC: 38260 AN: 151986 Hom.: 5275 Cov.: 32 AF XY: 0.254 AC XY: 18886 AN XY: 74280

African (AFR) AF: 0.125 AC: 5181 AN: 41458

American (AMR) AF: 0.311 AC: 4751 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.278 AC: 964 AN: 3472

East Asian (EAS) AF: 0.289 AC: 1493 AN: 5174

South Asian (SAS) AF: 0.347 AC: 1670 AN: 4810

European-Finnish (FIN) AF: 0.287 AC: 3025 AN: 10536

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

European-Non Finnish (NFE) AF: 0.298 AC: 20252 AN: 67948

Other (OTH) AF: 0.274 AC: 579 AN: 2110

Alfa AF: 0.286 Hom.: 29058

Bravo AF: 0.242

Asia WGS AF: 0.346 AC: 1203 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.2
DANN	Benign	0.71
PhyloP100		-0.46
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: rs10495447; hg19: chr1-240051340;