chr1-239735556-T-C

Position:

• chr1-239735556-T-C

Variant summary

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

The NM_001375978.1(CHRM3):​c.-147+57268T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.34 in 152,048 control chromosomes in the GnomAD database, including 10,428 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 0.34 (10428 hom., cov: 33)
• Consequence: CHRM3 NM_001375978.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.996

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-AS2 (HGNC:43725): (CHRM3 antisense RNA 2)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.447 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHRM3	NM_001375978.1	c.-147+57268T>C		intron_variant		ENST00000676153.1	NP_001362907.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHRM3	ENST00000676153.1	c.-147+57268T>C		intron_variant			NM_001375978.1	ENSP00000502667	P1

Frequencies

GnomAD3 genomes AF: 0.340 AC: 51600 AN: 151930 Hom.: 10419 Cov.: 33

Gnomad AFR AF: 0.111

Gnomad AMI AF: 0.521

Gnomad AMR AF: 0.439

Gnomad ASJ AF: 0.464

Gnomad EAS AF: 0.392

Gnomad SAS AF: 0.462

Gnomad FIN AF: 0.378

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.427

Gnomad OTH AF: 0.381

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

GnomAD4 genome AF: 0.340 AC: 51623 AN: 152048 Hom.: 10428 Cov.: 33 AF XY: 0.342 AC XY: 25406 AN XY: 74322

Gnomad4 AFR AF: 0.111

Gnomad4 AMR AF: 0.440

Gnomad4 ASJ AF: 0.464

Gnomad4 EAS AF: 0.392

Gnomad4 SAS AF: 0.463

Gnomad4 FIN AF: 0.378

Gnomad4 NFE AF: 0.427

Gnomad4 OTH AF: 0.381

Alfa AF: 0.372 Hom.: 1430

Bravo AF: 0.332

Asia WGS AF: 0.454 AC: 1580 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	6.0
DANN	Benign	0.85

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: rs1019882; hg19: chr1-239898856;