dbSNP rs10495449: CHRM3:c.*4084A>G (chr1-239913308-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001375978.1(CHRM3):c.*4084A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.316 in 166,896 control chromosomes in the GnomAD database, including 10,703 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 0.32 ( 10133 hom., cov: 32)

Exomes 𝑓: 0.27 ( 570 hom. )

Consequence

CHRM3
NM_001375978.1 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.214

Publications

7 publications found

Variant links:

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 links:

CHRM3-AS1 (HGNC:40150): (CHRM3 antisense RNA 1)

CHRM3-AS1 links:

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ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.591 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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CHRM3	NM_001375978.1	MANE Select	c.*4084A>G	3_prime_UTR	Exon 7 of 7	NP_001362907.1	P20309
CHRM3	NM_000740.4		c.*4084A>G	3_prime_UTR	Exon 5 of 5	NP_000731.1	P20309
CHRM3	NM_001347716.2		c.*4084A>G	3_prime_UTR	Exon 8 of 8	NP_001334645.1	P20309

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CHRM3	ENST00000676153.1	MANE Select	c.*4084A>G	3_prime_UTR	Exon 7 of 7	ENSP00000502667.1	P20309
CHRM3	ENST00000255380.8	TSL:1	c.*4084A>G	3_prime_UTR	Exon 5 of 5	ENSP00000255380.4	P20309
CHRM3-AS1	ENST00000827818.1		n.708+2463T>C	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.320

AC:

48653

AN:

151888

Hom.:

10097

Cov.:

show subpopulations

Gnomad AFR

AF:

0.596

Gnomad AMI

AF:

0.104

Gnomad AMR

AF:

0.242

Gnomad ASJ

AF:

0.115

Gnomad EAS

AF:

0.129

Gnomad SAS

AF:

0.216

Gnomad FIN

AF:

0.259

Gnomad MID

AF:

0.127

Gnomad NFE

AF:

0.218

Gnomad OTH

AF:

0.259

GnomAD4 exome

AF:

0.273

AC:

4068

AN:

14890

Hom.:

570

Cov.:

AF XY:

0.276

AC XY:

1952

AN XY:

7068

show subpopulations

African (AFR)

AF:

0.333

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.274

AC:

4035

AN:

14700

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.214

AC:

AN:

Other (OTH)

AF:

0.144

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

173

346

520

693

866

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.321

AC:

48739

AN:

152006

Hom.:

10133

Cov.:

AF XY:

0.318

AC XY:

23648

AN XY:

74314

show subpopulations

African (AFR)

AF:

0.597

AC:

24707

AN:

41392

American (AMR)

AF:

0.242

AC:

3692

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.115

AC:

399

AN:

3472

East Asian (EAS)

AF:

0.129

AC:

668

AN:

5164

South Asian (SAS)

AF:

0.213

AC:

1029

AN:

4820

European-Finnish (FIN)

AF:

0.259

AC:

2740

AN:

10582

Middle Eastern (MID)

AF:

0.133

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.218

AC:

14823

AN:

67978

Other (OTH)

AF:

0.259

AC:

547

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1451

2902

4353

5804

7255

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

444

888

1332

1776

2220

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.253

Hom.:

18980

Bravo

AF:

0.331

Asia WGS

AF:

0.202

AC:

708

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.63

(source)

DANN

Benign

0.54

PhyloP100

-0.21

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over