Variant rs2067480 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_000738.3(CHRM1):c.1353C>T(p.Ser451=) 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 1,614,016 control chromosomes in the GnomAD database, including 8,408 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 ( 940 hom., cov: 33)

Exomes 𝑓: 0.092 ( 7468 hom. )

Consequence

CHRM1
NM_000738.3 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.851

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:

(HGNC:):

links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP7

Synonymous conserved (PhyloP=-0.851 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
CHRM1	NM_000738.3 linkuse as main transcript	c.1353C>T	p.Ser451=	synonymous_variant	2/2	ENST00000306960.4
LOC124902683	XR_007062701.1 linkuse as main transcript	n.86+133G>A		intron_variant, non_coding_transcript_variant
CHRM1	XM_011544742.3 linkuse as main transcript	c.1353C>T	p.Ser451=	synonymous_variant	2/2
LOC124902683	XR_007062700.1 linkuse as main transcript	n.86+133G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHRM1	ENST00000306960.4 linkuse as main transcript	c.1353C>T	p.Ser451=	synonymous_variant	2/2	1	NM_000738.3	P1	P11229-1
	ENST00000543624.1 linkuse as main transcript	n.70+133G>A		intron_variant, non_coding_transcript_variant		3
CHRM1	ENST00000543973.1 linkuse as main transcript	c.1353C>T	p.Ser451=	synonymous_variant	3/3	5			P11229-2

Frequencies

GnomAD3 genomes

AF:

0.0882

AC:

13421

AN:

152222

Hom.:

938

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0202

Gnomad AMI

AF:

0.144

Gnomad AMR

AF:

0.232

Gnomad ASJ

AF:

0.0904

Gnomad EAS

AF:

0.0898

Gnomad SAS

AF:

0.0347

Gnomad FIN

AF:

0.146

Gnomad MID

AF:

0.127

Gnomad NFE

AF:

0.0909

Gnomad OTH

AF:

0.0889

GnomAD3 exomes

AF:

0.111

AC:

27895

AN:

250728

Hom.:

2326

AF XY:

0.104

AC XY:

14034

AN XY:

135494

show subpopulations

Gnomad AFR exome

AF:

0.0193

Gnomad AMR exome

AF:

0.273

Gnomad ASJ exome

AF:

0.0881

Gnomad EAS exome

AF:

0.0937

Gnomad SAS exome

AF:

0.0377

Gnomad FIN exome

AF:

0.148

Gnomad NFE exome

AF:

0.0926

Gnomad OTH exome

AF:

0.114

GnomAD4 exome

AF:

0.0917

AC:

134091

AN:

1461676

Hom.:

7468

Cov.:

AF XY:

0.0902

AC XY:

65619

AN XY:

727122

show subpopulations

Gnomad4 AFR exome

AF:

0.0178

Gnomad4 AMR exome

AF:

0.272

Gnomad4 ASJ exome

AF:

0.0901

Gnomad4 EAS exome

AF:

0.0814

Gnomad4 SAS exome

AF:

0.0377

Gnomad4 FIN exome

AF:

0.141

Gnomad4 NFE exome

AF:

0.0893

Gnomad4 OTH exome

AF:

0.0849

GnomAD4 genome

AF:

0.0882

AC:

13438

AN:

152340

Hom.:

940

Cov.:

AF XY:

0.0940

AC XY:

7002

AN XY:

74492

show subpopulations

Gnomad4 AFR

AF:

0.0201

Gnomad4 AMR

AF:

0.232

Gnomad4 ASJ

AF:

0.0904

Gnomad4 EAS

AF:

0.0904

Gnomad4 SAS

AF:

0.0345

Gnomad4 FIN

AF:

0.146

Gnomad4 NFE

AF:

0.0909

Gnomad4 OTH

AF:

0.0918

Alfa

AF:

0.0858

Hom.:

275

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

-0.82

CADD

Benign

1.0

DANN

Benign

0.90

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