rs2067482

Variant names:

• chr11-46385217-G-A
• rs2067482
• NM_000741.5:c.1341C>T

Your query was ambiguous. Multiple possible variants found:

• chr11-46385217-G-A
• chr11-46385217-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.74
• Publications: 19 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
CHRM4	NM_000741.5	c.1341C>T	p.Thr447Thr	synonymous_variant	Exon 2 of 2	ENST00000682254.1	NP_000732.2
CHRM4	NM_001366692.2	c.1341C>T	p.Thr447Thr	synonymous_variant	Exon 2 of 2		NP_001353621.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHRM4	ENST00000682254.1	c.1341C>T	p.Thr447Thr	synonymous_variant	Exon 2 of 2		NM_000741.5	ENSP00000507561.1
CHRM4	ENST00000433765.3	c.1341C>T	p.Thr447Thr	synonymous_variant	Exon 1 of 1	6		ENSP00000409378.2

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

GnomAD2 exomes AF: 0.134 AC: 33632 AN: 250384 AF XY: 0.139

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 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

African (AFR) AF: 0.105 AC: 3526 AN: 33480

American (AMR) AF: 0.0734 AC: 3281 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.162 AC: 4239 AN: 26136

East Asian (EAS) AF: 0.0577 AC: 2292 AN: 39696

South Asian (SAS) AF: 0.154 AC: 13245 AN: 86258

European-Finnish (FIN) AF: 0.120 AC: 6379 AN: 53312

Middle Eastern (MID) AF: 0.193 AC: 1114 AN: 5768

European-Non Finnish (NFE) AF: 0.168 AC: 186387 AN: 1111928

Other (OTH) AF: 0.154 AC: 9271 AN: 60382

GnomAD4 genome AF: 0.139 AC: 21190 AN: 152262 Hom.: 1551 Cov.: 33 AF XY: 0.137 AC XY: 10198 AN XY: 74454

African (AFR) AF: 0.111 AC: 4621 AN: 41546

American (AMR) AF: 0.108 AC: 1650 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.158 AC: 548 AN: 3472

East Asian (EAS) AF: 0.0582 AC: 302 AN: 5192

South Asian (SAS) AF: 0.147 AC: 712 AN: 4828

European-Finnish (FIN) AF: 0.117 AC: 1242 AN: 10612

Middle Eastern (MID) AF: 0.163 AC: 48 AN: 294

European-Non Finnish (NFE) AF: 0.169 AC: 11518 AN: 68008

Other (OTH) AF: 0.145 AC: 306 AN: 2112

Alfa AF: 0.153 Hom.: 840

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
PhyloP100		5.7
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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