rs2067482

chr11-46385217-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000741.5(CHRM4):c.1341C>T(p.Thr447=) 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.74

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]

ACMG classification

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	UniProt
CHRM4	NM_000741.5	c.1341C>T	p.Thr447=	synonymous_variant	2/2	ENST00000682254.1
CHRM4	NM_001366692.2	c.1341C>T	p.Thr447=	synonymous_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHRM4	ENST00000682254.1	c.1341C>T	p.Thr447=	synonymous_variant	2/2		NM_000741.5	P1
CHRM4	ENST00000433765.3	c.1341C>T	p.Thr447=	synonymous_variant	1/1			P1

Frequencies

GnomAD3 genomes AF: 0.139 AC: 21189 AN: 152144 Hom.: 1554 Cov.: 33

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

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.: 33 AF XY: 0.157 AC XY: 114510 AN XY: 727110

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.: 33 AF XY: 0.137 AC XY: 10198 AN XY: 74454

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

Other links and lift over

dbSNP: rs2067482; hg19: chr11-46406767; COSMIC: COSV58988404; COSMIC: COSV58988404;