rs11823728

chr11-62909330-C-T

Variant summary

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

The NM_000738.3(CHRM1):c.*388G>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 0.0501 in 196,386 control chromosomes in the GnomAD database, including 340 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 0.055 (302 hom., cov: 32)
  • Exomes 𝑓: 0.034 (38 hom.)
• Consequence: CHRM1 NM_000738.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.02

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.104 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHRM1	NM_000738.3	c.*388G>A		3_prime_UTR_variant	2/2	ENST00000306960.4
CHRM1	XM_011544742.3	c.*388G>A		3_prime_UTR_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHRM1	ENST00000306960.4	c.*388G>A		3_prime_UTR_variant	2/2	1	NM_000738.3	P1

Frequencies

GnomAD3 genomes AF: 0.0546 AC: 8311 AN: 152126 Hom.: 299 Cov.: 32

Gnomad AFR AF: 0.106

Gnomad AMI AF: 0.0362

Gnomad AMR AF: 0.0265

Gnomad ASJ AF: 0.100

Gnomad EAS AF: 0.00830

Gnomad SAS AF: 0.0765

Gnomad FIN AF: 0.0461

Gnomad MID AF: 0.0446

Gnomad NFE AF: 0.0308

Gnomad OTH AF: 0.0527

GnomAD4 exome AF: 0.0337 AC: 1488 AN: 44142 Hom.: 38 Cov.: 0 AF XY: 0.0360 AC XY: 813 AN XY: 22564

Gnomad4 AFR exome AF: 0.0954

Gnomad4 AMR exome AF: 0.0177

Gnomad4 ASJ exome AF: 0.0903

Gnomad4 EAS exome AF: 0.00520

Gnomad4 SAS exome AF: 0.0702

Gnomad4 FIN exome AF: 0.0323

Gnomad4 NFE exome AF: 0.0283

Gnomad4 OTH exome AF: 0.0394

GnomAD4 genome AF: 0.0548 AC: 8342 AN: 152244 Hom.: 302 Cov.: 32 AF XY: 0.0548 AC XY: 4081 AN XY: 74434

Gnomad4 AFR AF: 0.107

Gnomad4 AMR AF: 0.0265

Gnomad4 ASJ AF: 0.100

Gnomad4 EAS AF: 0.00851

Gnomad4 SAS AF: 0.0763

Gnomad4 FIN AF: 0.0461

Gnomad4 NFE AF: 0.0308

Gnomad4 OTH AF: 0.0545

Alfa AF: 0.0372 Hom.: 137

Bravo AF: 0.0540

Asia WGS AF: 0.0550 AC: 189 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.73
Dann	Benign	0.53

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: rs11823728; hg19: chr11-62676802;