1-239848453-A-C

Position:

• chr1-239848453-A-C

Variant summary

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

The NM_001375978.1(CHRM3):​c.-20+21075A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.189 in 152,014 control chromosomes in the GnomAD database, including 3,367 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 0.19 (3367 hom., cov: 32)
• Consequence: CHRM3 NM_001375978.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.473

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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.246 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHRM3	NM_001375978.1	c.-20+21075A>C		intron_variant		ENST00000676153.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHRM3	ENST00000676153.1	c.-20+21075A>C		intron_variant			NM_001375978.1	P1

Frequencies

GnomAD3 genomes AF: 0.189 AC: 28668 AN: 151896 Hom.: 3365 Cov.: 32

Gnomad AFR AF: 0.0494

Gnomad AMI AF: 0.271

Gnomad AMR AF: 0.245

Gnomad ASJ AF: 0.281

Gnomad EAS AF: 0.124

Gnomad SAS AF: 0.137

Gnomad FIN AF: 0.276

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.249

Gnomad OTH AF: 0.214

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

GnomAD4 genome AF: 0.189 AC: 28662 AN: 152014 Hom.: 3367 Cov.: 32 AF XY: 0.189 AC XY: 14028 AN XY: 74320

Gnomad4 AFR AF: 0.0493

Gnomad4 AMR AF: 0.245

Gnomad4 ASJ AF: 0.281

Gnomad4 EAS AF: 0.124

Gnomad4 SAS AF: 0.138

Gnomad4 FIN AF: 0.276

Gnomad4 NFE AF: 0.249

Gnomad4 OTH AF: 0.214

Alfa AF: 0.234 Hom.: 5260

Bravo AF: 0.181

Asia WGS AF: 0.125 AC: 434 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.7
DANN	Benign	0.45

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: rs1594513; hg19: chr1-240011753;