1-239828986-G-A

Variant names:

• chr1-239828986-G-A
• rs621060
• NM_001375978.1:c.-20+1608G>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.-20+1608G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.784 in 152,098 control chromosomes in the GnomAD database, including 48,426 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 0.78 (48426 hom., cov: 31)
• Consequence: CHRM3 NM_001375978.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.524
• Publications: 5 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 = 0.97 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHRM3	NM_001375978.1	MANE Select	c.-20+1608G>A		intron	N/A	NP_001362907.1
	CHRM3	NM_000740.4		c.-20+1608G>A		intron	N/A	NP_000731.1
	CHRM3	NM_001347716.2		c.-20+1608G>A		intron	N/A	NP_001334645.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHRM3	ENST00000676153.1	MANE Select	c.-20+1608G>A		intron	N/A	ENSP00000502667.1
	CHRM3	ENST00000255380.8	TSL:1	c.-20+1608G>A		intron	N/A	ENSP00000255380.4
	CHRM3	ENST00000615928.5	TSL:5	c.-20+1608G>A		intron	N/A	ENSP00000482377.1

Frequencies

GnomAD3 genomes AF: 0.784 AC: 119141 AN: 151980 Hom.: 48410 Cov.: 31

Gnomad AFR AF: 0.552

Gnomad AMI AF: 0.866

Gnomad AMR AF: 0.876

Gnomad ASJ AF: 0.822

Gnomad EAS AF: 0.993

Gnomad SAS AF: 0.953

Gnomad FIN AF: 0.881

Gnomad MID AF: 0.845

Gnomad NFE AF: 0.857

Gnomad OTH AF: 0.804

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

GnomAD4 genome AF: 0.784 AC: 119196 AN: 152098 Hom.: 48426 Cov.: 31 AF XY: 0.791 AC XY: 58817 AN XY: 74368

African (AFR) AF: 0.552 AC: 22848 AN: 41420

American (AMR) AF: 0.876 AC: 13400 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.822 AC: 2851 AN: 3470

East Asian (EAS) AF: 0.993 AC: 5132 AN: 5168

South Asian (SAS) AF: 0.954 AC: 4601 AN: 4824

European-Finnish (FIN) AF: 0.881 AC: 9342 AN: 10606

Middle Eastern (MID) AF: 0.844 AC: 248 AN: 294

European-Non Finnish (NFE) AF: 0.857 AC: 58290 AN: 67994

Other (OTH) AF: 0.801 AC: 1694 AN: 2116

Alfa AF: 0.842 Hom.: 98317

Bravo AF: 0.773

Asia WGS AF: 0.943 AC: 3279 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.25
DANN	Benign	0.61
PhyloP100		-0.52
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs621060; hg19: chr1-239992286;