NM_001375978.1:c.-147+49923T>A

Variant names:

• chr1-239728211-T-A
• rs6657343
• NM_001375978.1:c.-147+49923T>A

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+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
• Publications: 3 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.66 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001375978.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHRM3	NM_001375978.1	MANE Select	c.-147+49923T>A		intron	N/A	NP_001362907.1
	CHRM3	NM_000740.4		c.-147+49923T>A		intron	N/A	NP_000731.1
	CHRM3	NM_001347716.2		c.-376+49923T>A		intron	N/A	NP_001334645.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHRM3	ENST00000676153.1	MANE Select	c.-147+49923T>A		intron	N/A	ENSP00000502667.1
	CHRM3	ENST00000255380.8	TSL:1	c.-147+49923T>A		intron	N/A	ENSP00000255380.4
	CHRM3	ENST00000615928.5	TSL:5	c.-147+49923T>A		intron	N/A	ENSP00000482377.1

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

African (AFR) AF: 0.667 AC: 27640 AN: 41468

American (AMR) AF: 0.583 AC: 8874 AN: 15210

Ashkenazi Jewish (ASJ) AF: 0.559 AC: 1938 AN: 3464

East Asian (EAS) AF: 0.471 AC: 2399 AN: 5092

South Asian (SAS) AF: 0.521 AC: 2506 AN: 4814

European-Finnish (FIN) AF: 0.446 AC: 4719 AN: 10584

Middle Eastern (MID) AF: 0.544 AC: 160 AN: 294

European-Non Finnish (NFE) AF: 0.511 AC: 34670 AN: 67852

Other (OTH) AF: 0.553 AC: 1166 AN: 2110

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.8
DANN	Benign	0.36
PhyloP100		0.33
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: rs6657343; hg19: chr1-239891511;