Genetic Variant CHRM1:c.-79+3153G>A (chr11-62918065-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_000738.3(CHRM1):c.-79+3153G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.787 in 152,072 control chromosomes in the GnomAD database, including 47,692 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 0.79 ( 47648 hom., cov: 29)

Exomes 𝑓: 0.70 ( 44 hom. )

Consequence

CHRM1
NM_000738.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0680

Publications

9 publications found

Variant links:

Genes affected

CHRM1 (HGNC:1950): (cholinergic receptor muscarinic 1) 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 1 is involved in mediation of vagally-induced bronchoconstriction and in the acid secretion of the gastrointestinal tract. The gene encoding this receptor is localized to 11q13. [provided by RefSeq, Jul 2008]

CHRM1 Gene-Disease associations (from GenCC):

intellectual disability
Inheritance: AD Classification: LIMITED Submitted by: G2P

CHRM1 links:

ENSG00000257002 (HGNC:58194):

ENSG00000257002 links:

Genome browser will be placed here

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=-0.87).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.918 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
CHRM1	NM_000738.3 link	c.-79+3153G>A	intron_variant	Intron 1 of 1	ENST00000306960.4	NP_000729.2
CHRM1-AS1	NR_199052.1 link	n.592C>T	non_coding_transcript_exon_variant	Exon 3 of 3
CHRM1	XM_011544742.3 link	c.-79+3773G>A	intron_variant	Intron 1 of 1		XP_011543044.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHRM1	ENST00000306960.4 link	c.-79+3153G>A		intron_variant	Intron 1 of 1	1	NM_000738.3	ENSP00000306490.3

Frequencies

GnomAD3 genomes

AF:

0.787

AC:

119383

AN:

151776

Hom.:

47587

Cov.:

show subpopulations

Gnomad AFR

AF:

0.925

Gnomad AMI

AF:

0.757

Gnomad AMR

AF:

0.782

Gnomad ASJ

AF:

0.775

Gnomad EAS

AF:

0.859

Gnomad SAS

AF:

0.802

Gnomad FIN

AF:

0.776

Gnomad MID

AF:

0.766

Gnomad NFE

AF:

0.700

Gnomad OTH

AF:

0.754

GnomAD4 exome

AF:

0.697

AC:

124

AN:

178

Hom.:

Cov.:

AF XY:

0.674

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

1.00

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AF:

1.00

AC:

AN:

European-Finnish (FIN)

AF:

0.711

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.630

AC:

AN:

Other (OTH)

AF:

0.727

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.787

AC:

119502

AN:

151894

Hom.:

47648

Cov.:

AF XY:

0.791

AC XY:

58705

AN XY:

74228

show subpopulations

African (AFR)

AF:

0.926

AC:

38367

AN:

41446

American (AMR)

AF:

0.782

AC:

11937

AN:

15260

Ashkenazi Jewish (ASJ)

AF:

0.775

AC:

2691

AN:

3472

East Asian (EAS)

AF:

0.859

AC:

4427

AN:

5156

South Asian (SAS)

AF:

0.801

AC:

3839

AN:

4792

European-Finnish (FIN)

AF:

0.776

AC:

8184

AN:

10540

Middle Eastern (MID)

AF:

0.762

AC:

224

AN:

294

European-Non Finnish (NFE)

AF:

0.700

AC:

47549

AN:

67912

Other (OTH)

AF:

0.755

AC:

1594

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

1197

2394

3592

4789

5986

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

862

1724

2586

3448

4310

<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:

0.756

Hom.:

15570

Bravo

AF:

0.793

Asia WGS

AF:

0.824

AC:

2867

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

2.6

(source)

DANN

Benign

0.75

PhyloP100

0.068

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over