1-239819090-C-T

Position:

• chr1-239819090-C-T

Variant summary

Our verdict is Benign. Variant got -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

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHRM3	NM_001375978.1	c.-146-8162C>T		intron_variant		ENST00000676153.1	NP_001362907.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHRM3	ENST00000676153.1	c.-146-8162C>T		intron_variant			NM_001375978.1	ENSP00000502667.1

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

Gnomad4 AFR AF: 0.209

Gnomad4 AMR AF: 0.211

Gnomad4 ASJ AF: 0.214

Gnomad4 EAS AF: 0.175

Gnomad4 SAS AF: 0.221

Gnomad4 FIN AF: 0.171

Gnomad4 NFE AF: 0.187

Gnomad4 OTH AF: 0.209

Alfa AF: 0.191 Hom.: 2811

Bravo AF: 0.196

Asia WGS AF: 0.208 AC: 724 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.3
DANN	Benign	0.67

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

Publications

LitVar

Other links and lift over

dbSNP: rs1072319; hg19: chr1-239982390;