rs72910092

Positions:

• chr11-46384943-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_000741.5(CHRM4):​c.*175G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0187 in 645,342 control chromosomes in the GnomAD database, including 141 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 0.016 (22 hom., cov: 33)
  • Exomes 𝑓: 0.020 (119 hom.)
• Consequence: CHRM4 NM_000741.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.86

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=-0.6).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0161 (2454/152352) while in subpopulation NFE AF= 0.0219 (1492/68028). AF 95% confidence interval is 0.021. There are 22 homozygotes in gnomad4. There are 1264 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 2454 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHRM4	NM_000741.5	c.*175G>A		3_prime_UTR_variant	2/2	ENST00000682254.1
CHRM4	NM_001366692.2	c.*175G>A		3_prime_UTR_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHRM4	ENST00000682254.1	c.*175G>A		3_prime_UTR_variant	2/2		NM_000741.5	P1

Frequencies

GnomAD3 genomes AF: 0.0161 AC: 2456 AN: 152234 Hom.: 22 Cov.: 33

Gnomad AFR AF: 0.00376

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0200

Gnomad ASJ AF: 0.00374

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.0429

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0219

Gnomad OTH AF: 0.0143

GnomAD4 exome AF: 0.0196 AC: 9643 AN: 492990 Hom.: 119 AF XY: 0.0196 AC XY: 4534 AN XY: 231106

Gnomad4 AFR exome AF: 0.00154

Gnomad4 AMR exome AF: 0.00178

Gnomad4 ASJ exome AF: 0.00234

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000725

Gnomad4 FIN exome AF: 0.0130

Gnomad4 NFE exome AF: 0.0207

Gnomad4 OTH exome AF: 0.0155

GnomAD4 genome AF: 0.0161 AC: 2454 AN: 152352 Hom.: 22 Cov.: 33 AF XY: 0.0170 AC XY: 1264 AN XY: 74502

Gnomad4 AFR AF: 0.00375

Gnomad4 AMR AF: 0.0199

Gnomad4 ASJ AF: 0.00374

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.0429

Gnomad4 NFE AF: 0.0219

Gnomad4 OTH AF: 0.0142

Alfa AF: 0.0195 Hom.: 3

Bravo AF: 0.0135

Asia WGS AF: 0.00173 AC: 6 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	0.79
DANN	Benign	0.84

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs72910092; hg19: chr11-46406493;