1-239819090-C-T

Variant names:

• chr1-239819090-C-T
• rs1072319
• NM_001375978.1:c.-146-8162C>T

Variant summary

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

The NM_001375978.1(CHRM3):​c.-146-8162C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.195 in 152,130 control chromosomes in the GnomAD database, including 2,921 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 (2921 hom., cov: 32)
• Consequence: CHRM3 NM_001375978.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.247
• 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=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.21 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.-146-8162C>T		intron	N/A	NP_001362907.1	P20309
	CHRM3	NM_000740.4		c.-146-8162C>T		intron	N/A	NP_000731.1	P20309
	CHRM3	NM_001347716.2		c.-375-7763C>T		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.-146-8162C>T		intron	N/A	ENSP00000502667.1	P20309
	CHRM3	ENST00000255380.8	TSL:1	c.-146-8162C>T		intron	N/A	ENSP00000255380.4	P20309
	CHRM3	ENST00000615928.5	TSL:5	c.-146-8162C>T		intron	N/A	ENSP00000482377.1	P20309

Frequencies

GnomAD3 genomes AF: 0.195 AC: 29684 AN: 152012 Hom.: 2924 Cov.: 32

Gnomad AFR AF: 0.209

Gnomad AMI AF: 0.105

Gnomad AMR AF: 0.212

Gnomad ASJ AF: 0.214

Gnomad EAS AF: 0.174

Gnomad SAS AF: 0.221

Gnomad FIN AF: 0.171

Gnomad MID AF: 0.190

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: 0.195 AC: 29691 AN: 152130 Hom.: 2921 Cov.: 32 AF XY: 0.195 AC XY: 14473 AN XY: 74350

African (AFR) AF: 0.209 AC: 8665 AN: 41508

American (AMR) AF: 0.211 AC: 3226 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.214 AC: 743 AN: 3468

East Asian (EAS) AF: 0.175 AC: 899 AN: 5150

South Asian (SAS) AF: 0.221 AC: 1066 AN: 4826

European-Finnish (FIN) AF: 0.171 AC: 1816 AN: 10590

Middle Eastern (MID) AF: 0.187 AC: 55 AN: 294

European-Non Finnish (NFE) AF: 0.187 AC: 12683 AN: 67994

Other (OTH) AF: 0.209 AC: 442 AN: 2112

Alfa AF: 0.192 Hom.: 2969

Bravo AF: 0.196

Asia WGS AF: 0.208 AC: 724 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.3
DANN	Benign	0.67
PhyloP100		-0.25
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: rs1072319; hg19: chr1-239982390;