dbSNP rs2067477: CHRM1:p.Gly89Gly (chr11-62910834-G-T) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_ModerateBP7BA1

The NM_000738.3(CHRM1):c.267C>A(p.Gly89Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0914 in 1,614,004 control chromosomes in the GnomAD database, including 8,404 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 0.088 ( 935 hom., cov: 32)

Exomes 𝑓: 0.092 ( 7469 hom. )

Consequence

CHRM1
NM_000738.3 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.40

Publications

29 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 -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.44).

BP7

Synonymous conserved (PhyloP=3.4 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.226 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHRM1	NM_000738.3 link	c.267C>A	p.Gly89Gly	synonymous_variant	Exon 2 of 2	ENST00000306960.4	NP_000729.2	P11229-1Q53XZ3
CHRM1	XM_011544742.3 link	c.267C>A	p.Gly89Gly	synonymous_variant	Exon 2 of 2		XP_011543044.1	P11229-1Q53XZ3
CHRM1-AS1	NR_199052.1 link	n.441G>T		non_coding_transcript_exon_variant	Exon 2 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHRM1	ENST00000306960.4 link	c.267C>A	p.Gly89Gly	synonymous_variant	Exon 2 of 2	1	NM_000738.3	ENSP00000306490.3		P11229-1

Frequencies

GnomAD3 genomes

AF:

0.0881

AC:

13399

AN:

152054

Hom.:

933

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0199

Gnomad AMI

AF:

0.144

Gnomad AMR

AF:

0.232

Gnomad ASJ

AF:

0.0902

Gnomad EAS

AF:

0.0905

Gnomad SAS

AF:

0.0344

Gnomad FIN

AF:

0.145

Gnomad MID

AF:

0.127

Gnomad NFE

AF:

0.0910

Gnomad OTH

AF:

0.0887

GnomAD2 exomes

AF:

0.111

AC:

27945

AN:

251330

AF XY:

0.104

show subpopulations

Gnomad AFR exome

AF:

0.0192

Gnomad AMR exome

AF:

0.273

Gnomad ASJ exome

AF:

0.0876

Gnomad EAS exome

AF:

0.0947

Gnomad FIN exome

AF:

0.148

Gnomad NFE exome

AF:

0.0926

Gnomad OTH exome

AF:

0.114

GnomAD4 exome

AF:

0.0917

AC:

134109

AN:

1461832

Hom.:

7469

Cov.:

AF XY:

0.0902

AC XY:

65623

AN XY:

727222

show subpopulations

African (AFR)

AF:

0.0178

AC:

596

AN:

33480

American (AMR)

AF:

0.272

AC:

12155

AN:

44696

Ashkenazi Jewish (ASJ)

AF:

0.0896

AC:

2341

AN:

26136

East Asian (EAS)

AF:

0.0818

AC:

3247

AN:

39700

South Asian (SAS)

AF:

0.0377

AC:

3253

AN:

86258

European-Finnish (FIN)

AF:

0.141

AC:

7541

AN:

53416

Middle Eastern (MID)

AF:

0.0988

AC:

570

AN:

5768

European-Non Finnish (NFE)

AF:

0.0893

AC:

99271

AN:

1111984

Other (OTH)

AF:

0.0850

AC:

5135

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

7779

15558

23338

31117

38896

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3664

7328

10992

14656

18320

<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:

0.0882

AC:

13416

AN:

152172

Hom.:

935

Cov.:

AF XY:

0.0939

AC XY:

6988

AN XY:

74408

show subpopulations

African (AFR)

AF:

0.0199

AC:

828

AN:

41532

American (AMR)

AF:

0.232

AC:

3551

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.0902

AC:

313

AN:

3470

East Asian (EAS)

AF:

0.0911

AC:

472

AN:

5182

South Asian (SAS)

AF:

0.0342

AC:

165

AN:

4822

European-Finnish (FIN)

AF:

0.145

AC:

1538

AN:

10574

Middle Eastern (MID)

AF:

0.126

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0910

AC:

6188

AN:

67990

Other (OTH)

AF:

0.0916

AC:

193

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

591

1181

1772

2362

2953

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

138

276

414

552

690

<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:

0.0903

Hom.:

1570

Bravo

AF:

0.0930

Asia WGS

AF:

0.0690

AC:

240

AN:

3478

EpiCase

AF:

0.0884

EpiControl

AF:

0.0818

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.44

CADD

Benign

(source)

DANN

Benign

0.89

PhyloP100

3.4

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