chr1-239669380-C-T

Variant names:

• chr1-239669380-C-T
• rs10802789
• NM_001375978.1:c.-249-8806C>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.-249-8806C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.439 in 151,952 control chromosomes in the GnomAD database, including 15,486 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 0.44 (15486 hom., cov: 32)
• Consequence: CHRM3 NM_001375978.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.443
• Publications: 11 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 (EAS) allele frequency at 95% confidence interval = 0.69 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHRM3	NM_001375978.1	c.-249-8806C>T		intron_variant	Intron 4 of 6	ENST00000676153.1	NP_001362907.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHRM3	ENST00000676153.1	c.-249-8806C>T		intron_variant	Intron 4 of 6		NM_001375978.1	ENSP00000502667.1

Frequencies

GnomAD3 genomes AF: 0.439 AC: 66723 AN: 151834 Hom.: 15479 Cov.: 32

Gnomad AFR AF: 0.332

Gnomad AMI AF: 0.405

Gnomad AMR AF: 0.527

Gnomad ASJ AF: 0.347

Gnomad EAS AF: 0.709

Gnomad SAS AF: 0.316

Gnomad FIN AF: 0.553

Gnomad MID AF: 0.306

Gnomad NFE AF: 0.462

Gnomad OTH AF: 0.436

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

GnomAD4 genome AF: 0.439 AC: 66738 AN: 151952 Hom.: 15486 Cov.: 32 AF XY: 0.443 AC XY: 32911 AN XY: 74274

African (AFR) AF: 0.331 AC: 13720 AN: 41422

American (AMR) AF: 0.528 AC: 8071 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.347 AC: 1204 AN: 3472

East Asian (EAS) AF: 0.709 AC: 3668 AN: 5170

South Asian (SAS) AF: 0.315 AC: 1514 AN: 4810

European-Finnish (FIN) AF: 0.553 AC: 5821 AN: 10528

Middle Eastern (MID) AF: 0.301 AC: 88 AN: 292

European-Non Finnish (NFE) AF: 0.462 AC: 31369 AN: 67962

Other (OTH) AF: 0.433 AC: 914 AN: 2112

Alfa AF: 0.445 Hom.: 24913

Bravo AF: 0.441

Asia WGS AF: 0.429 AC: 1491 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.28
DANN	Benign	0.44
PhyloP100		-0.44
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: rs10802789; hg19: chr1-239832680;