Variant rs2067477 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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

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 links:

ENSG00000257002 (HGNC:):

ENSG00000257002 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
CHRM1	NM_000738.3 linkuse as main transcript	c.267C>A	p.Gly89Gly	synonymous_variant	2/2	ENST00000306960.4	NP_000729.2	P11229-1Q53XZ3
CHRM1	XM_011544742.3 linkuse as main transcript	c.267C>A	p.Gly89Gly	synonymous_variant	2/2		XP_011543044.1	P11229-1Q53XZ3
LOC124902683	XR_007062700.1 linkuse as main transcript	n.318G>T		non_coding_transcript_exon_variant	2/3
LOC124902683	XR_007062701.1 linkuse as main transcript	n.318G>T		non_coding_transcript_exon_variant	2/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CHRM1	ENST00000306960.4 linkuse as main transcript	c.267C>A	p.Gly89Gly	synonymous_variant	2/2	1	NM_000738.3	ENSP00000306490.3	P11229-1
CHRM1	ENST00000543973.1 linkuse as main transcript	c.267C>A	p.Gly89Gly	synonymous_variant	3/3	5		ENSP00000441188.1	P11229-2
CHRM1	ENST00000536524.1 linkuse as main transcript	c.267C>A	p.Gly89Gly	synonymous_variant	2/2	4		ENSP00000444482.1	F5GZF8
ENSG00000257002	ENST00000543624.1 linkuse as main transcript	n.302G>T		non_coding_transcript_exon_variant	2/3	3

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

GnomAD3 exomes

AF:

0.111

AC:

27945

AN:

251330

Hom.:

2319

AF XY:

0.104

AC XY:

14063

AN XY:

135854

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 SAS exome

AF:

0.0376

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

Gnomad4 AFR exome

AF:

0.0178

Gnomad4 AMR exome

AF:

0.272

Gnomad4 ASJ exome

AF:

0.0896

Gnomad4 EAS exome

AF:

0.0818

Gnomad4 SAS exome

AF:

0.0377

Gnomad4 FIN exome

AF:

0.141

Gnomad4 NFE exome

AF:

0.0893

Gnomad4 OTH exome

AF:

0.0850

GnomAD4 genome

AF:

0.0882

AC:

13416

AN:

152172

Hom.:

935

Cov.:

AF XY:

0.0939

AC XY:

6988

AN XY:

74408

show subpopulations

Gnomad4 AFR

AF:

0.0199

Gnomad4 AMR

AF:

0.232

Gnomad4 ASJ

AF:

0.0902

Gnomad4 EAS

AF:

0.0911

Gnomad4 SAS

AF:

0.0342

Gnomad4 FIN

AF:

0.145

Gnomad4 NFE

AF:

0.0910

Gnomad4 OTH

AF:

0.0916

Alfa

AF:

0.0890

Hom.:

1105

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

DANN

Benign

0.89

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over