rs621060

Positions:

• chr1-239828986-G-A
• chr1-239828986-G-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+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

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 (EAS) allele frequency at 95% confidence interval = 0.97 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHRM3	NM_001375978.1	c.-20+1608G>A		intron_variant		ENST00000676153.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHRM3	ENST00000676153.1	c.-20+1608G>A		intron_variant			NM_001375978.1	P1

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

Gnomad4 AFR AF: 0.552

Gnomad4 AMR AF: 0.876

Gnomad4 ASJ AF: 0.822

Gnomad4 EAS AF: 0.993

Gnomad4 SAS AF: 0.954

Gnomad4 FIN AF: 0.881

Gnomad4 NFE AF: 0.857

Gnomad4 OTH AF: 0.801

Alfa AF: 0.850 Hom.: 73772

Bravo AF: 0.773

Asia WGS AF: 0.943 AC: 3279 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.25
DANN	Benign	0.61

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

Publications

LitVar

Other links and lift over

dbSNP: rs621060; hg19: chr1-239992286;