1-239903960-G-A

Position:

• chr1-239903960-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001375978.1(CHRM3):​c.-19-3473G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.595 in 152,036 control chromosomes in the GnomAD database, including 27,476 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 0.59 (27476 hom., cov: 32)
• Consequence: CHRM3 NM_001375978.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.354

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]

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 (AFR) allele frequency at 95% confidence interval = 0.698 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHRM3	NM_001375978.1	c.-19-3473G>A		intron_variant		ENST00000676153.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHRM3	ENST00000676153.1	c.-19-3473G>A		intron_variant			NM_001375978.1	P1

Frequencies

GnomAD3 genomes AF: 0.595 AC: 90319 AN: 151918 Hom.: 27443 Cov.: 32

Gnomad AFR AF: 0.705

Gnomad AMI AF: 0.559

Gnomad AMR AF: 0.541

Gnomad ASJ AF: 0.466

Gnomad EAS AF: 0.479

Gnomad SAS AF: 0.529

Gnomad FIN AF: 0.698

Gnomad MID AF: 0.456

Gnomad NFE AF: 0.545

Gnomad OTH AF: 0.564

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

GnomAD4 genome AF: 0.595 AC: 90408 AN: 152036 Hom.: 27476 Cov.: 32 AF XY: 0.597 AC XY: 44368 AN XY: 74312

Gnomad4 AFR AF: 0.705

Gnomad4 AMR AF: 0.541

Gnomad4 ASJ AF: 0.466

Gnomad4 EAS AF: 0.479

Gnomad4 SAS AF: 0.527

Gnomad4 FIN AF: 0.698

Gnomad4 NFE AF: 0.545

Gnomad4 OTH AF: 0.565

Alfa AF: 0.543 Hom.: 47257

Bravo AF: 0.588

Asia WGS AF: 0.515 AC: 1795 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	2.4
DANN	Benign	0.38

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: rs7520974; hg19: chr1-240067260;