rs717227

Variant names:

• chr1-239719299-C-T
• rs717227
• NM_001375978.1:c.-147+41011C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001375978.1(CHRM3):​c.-147+41011C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.507 in 151,722 control chromosomes in the GnomAD database, including 19,738 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 0.51 (19738 hom., cov: 31)
• Consequence: CHRM3 NM_001375978.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.156
• Publications: 5 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.552 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHRM3	NM_001375978.1	c.-147+41011C>T		intron_variant	Intron 5 of 6	ENST00000676153.1	NP_001362907.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHRM3	ENST00000676153.1	c.-147+41011C>T		intron_variant	Intron 5 of 6		NM_001375978.1	ENSP00000502667.1

Frequencies

GnomAD3 genomes AF: 0.507 AC: 76855 AN: 151604 Hom.: 19711 Cov.: 31

Gnomad AFR AF: 0.494

Gnomad AMI AF: 0.564

Gnomad AMR AF: 0.562

Gnomad ASJ AF: 0.552

Gnomad EAS AF: 0.472

Gnomad SAS AF: 0.518

Gnomad FIN AF: 0.446

Gnomad MID AF: 0.532

Gnomad NFE AF: 0.510

Gnomad OTH AF: 0.516

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

GnomAD4 genome AF: 0.507 AC: 76927 AN: 151722 Hom.: 19738 Cov.: 31 AF XY: 0.506 AC XY: 37507 AN XY: 74142

African (AFR) AF: 0.494 AC: 20455 AN: 41382

American (AMR) AF: 0.562 AC: 8544 AN: 15192

Ashkenazi Jewish (ASJ) AF: 0.552 AC: 1917 AN: 3472

East Asian (EAS) AF: 0.471 AC: 2414 AN: 5126

South Asian (SAS) AF: 0.519 AC: 2496 AN: 4812

European-Finnish (FIN) AF: 0.446 AC: 4709 AN: 10562

Middle Eastern (MID) AF: 0.531 AC: 156 AN: 294

European-Non Finnish (NFE) AF: 0.511 AC: 34646 AN: 67866

Other (OTH) AF: 0.511 AC: 1076 AN: 2104

Alfa AF: 0.511 Hom.: 39729

Bravo AF: 0.514

Asia WGS AF: 0.515 AC: 1794 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.1
DANN	Benign	0.32
PhyloP100		-0.16
PromoterAI		0.0086	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs717227; hg19: chr1-239882599;