Variant rs2067482 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000741.5(CHRM4):c.1341C>T(p.Thr447Thr) variant causes a synonymous change. The variant allele was found at a frequency of 0.155 in 1,613,938 control chromosomes in the GnomAD database, including 20,553 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 0.14 ( 1551 hom., cov: 33)

Exomes 𝑓: 0.16 ( 19002 hom. )

Consequence

CHRM4
NM_000741.5 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.74

Variant links:

Genes affected

CHRM4 (HGNC:1953): (cholinergic receptor muscarinic 4) 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 clinical implications of this receptor are unknown; however, mouse studies link its function to adenylyl cyclase inhibition. [provided by RefSeq, Jul 2008]

CHRM4 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.48).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.167 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHRM4	NM_000741.5 linkuse as main transcript	c.1341C>T	p.Thr447Thr	synonymous_variant	2/2	ENST00000682254.1	NP_000732.2	P08173
CHRM4	NM_001366692.2 linkuse as main transcript	c.1341C>T	p.Thr447Thr	synonymous_variant	2/2		NP_001353621.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHRM4	ENST00000682254.1 linkuse as main transcript	c.1341C>T	p.Thr447Thr	synonymous_variant	2/2		NM_000741.5	ENSP00000507561.1		P08173
CHRM4	ENST00000433765.3 linkuse as main transcript	c.1341C>T	p.Thr447Thr	synonymous_variant	1/1	6		ENSP00000409378.2		P08173

Frequencies

GnomAD3 genomes

AF:

0.139

AC:

21189

AN:

152144

Hom.:

1554

Cov.:

show subpopulations

Gnomad AFR

AF:

0.111

Gnomad AMI

AF:

0.268

Gnomad AMR

AF:

0.108

Gnomad ASJ

AF:

0.158

Gnomad EAS

AF:

0.0582

Gnomad SAS

AF:

0.148

Gnomad FIN

AF:

0.117

Gnomad MID

AF:

0.158

Gnomad NFE

AF:

0.169

Gnomad OTH

AF:

0.148

GnomAD3 exomes

AF:

0.134

AC:

33632

AN:

250384

Hom.:

2521

AF XY:

0.139

AC XY:

18787

AN XY:

135578

show subpopulations

Gnomad AFR exome

AF:

0.109

Gnomad AMR exome

AF:

0.0690

Gnomad ASJ exome

AF:

0.162

Gnomad EAS exome

AF:

0.0562

Gnomad SAS exome

AF:

0.150

Gnomad FIN exome

AF:

0.113

Gnomad NFE exome

AF:

0.167

Gnomad OTH exome

AF:

0.149

GnomAD4 exome

AF:

0.157

AC:

229734

AN:

1461676

Hom.:

19002

Cov.:

AF XY:

0.157

AC XY:

114510

AN XY:

727110

show subpopulations

Gnomad4 AFR exome

AF:

0.105

Gnomad4 AMR exome

AF:

0.0734

Gnomad4 ASJ exome

AF:

0.162

Gnomad4 EAS exome

AF:

0.0577

Gnomad4 SAS exome

AF:

0.154

Gnomad4 FIN exome

AF:

0.120

Gnomad4 NFE exome

AF:

0.168

Gnomad4 OTH exome

AF:

0.154

GnomAD4 genome

AF:

0.139

AC:

21190

AN:

152262

Hom.:

1551

Cov.:

AF XY:

0.137

AC XY:

10198

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.111

Gnomad4 AMR

AF:

0.108

Gnomad4 ASJ

AF:

0.158

Gnomad4 EAS

AF:

0.0582

Gnomad4 SAS

AF:

0.147

Gnomad4 FIN

AF:

0.117

Gnomad4 NFE

AF:

0.169

Gnomad4 OTH

AF:

0.145

Alfa

AF:

0.154

Hom.:

834

Bravo

AF:

0.136

Asia WGS

AF:

0.100

AC:

346

AN:

3478

EpiCase

AF:

0.162

EpiControl

AF:

0.166

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.48

CADD

Benign

9.4

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