rs6657343

Positions:

• chr1-239728211-T-A
• chr1-239728211-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+49923T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.557 in 151,798 control chromosomes in the GnomAD database, including 24,183 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 0.56 (24183 hom., cov: 32)
• Consequence: CHRM3 NM_001375978.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.334

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.66 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHRM3	NM_001375978.1	c.-147+49923T>A		intron_variant		ENST00000676153.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHRM3	ENST00000676153.1	c.-147+49923T>A		intron_variant			NM_001375978.1	P1
CHRM3-AS2	ENST00000600831.5	n.65+2190A>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.557 AC: 84481 AN: 151680 Hom.: 24138 Cov.: 32

Gnomad AFR AF: 0.666

Gnomad AMI AF: 0.565

Gnomad AMR AF: 0.583

Gnomad ASJ AF: 0.559

Gnomad EAS AF: 0.472

Gnomad SAS AF: 0.520

Gnomad FIN AF: 0.446

Gnomad MID AF: 0.544

Gnomad NFE AF: 0.511

Gnomad OTH AF: 0.554

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

GnomAD4 genome AF: 0.557 AC: 84586 AN: 151798 Hom.: 24183 Cov.: 32 AF XY: 0.555 AC XY: 41157 AN XY: 74166

Gnomad4 AFR AF: 0.667

Gnomad4 AMR AF: 0.583

Gnomad4 ASJ AF: 0.559

Gnomad4 EAS AF: 0.471

Gnomad4 SAS AF: 0.521

Gnomad4 FIN AF: 0.446

Gnomad4 NFE AF: 0.511

Gnomad4 OTH AF: 0.553

Alfa AF: 0.536 Hom.: 2781

Bravo AF: 0.572

Asia WGS AF: 0.547 AC: 1906 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.8
DANN	Benign	0.36

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: rs6657343; hg19: chr1-239891511;