rs11823728

Variant names:

• chr11-62909330-C-T
• rs11823728
• NM_000738.3:c.*388G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 publications found

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]

CHRM1 Gene-Disease associations (from GenCC):

• intellectual disability

  Inheritance: AD Classification: LIMITED Submitted by: G2P

ENSG00000257002 (HGNC:58194):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000738.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHRM1	NM_000738.3	MANE Select	c.*388G>A		3_prime_UTR	Exon 2 of 2	NP_000729.2
	CHRM1-AS1	NR_199052.1		n.-77C>T		upstream_gene	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHRM1	ENST00000306960.4	TSL:1 MANE Select	c.*388G>A		3_prime_UTR	Exon 2 of 2	ENSP00000306490.3
	ENSG00000257002	ENST00000543624.2	TSL:3	n.-124C>T		upstream_gene	N/A
	ENSG00000257002	ENST00000782435.1		n.-190C>T		upstream_gene	N/A

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

African (AFR) AF: 0.0954 AC: 104 AN: 1090

American (AMR) AF: 0.0177 AC: 63 AN: 3550

Ashkenazi Jewish (ASJ) AF: 0.0903 AC: 102 AN: 1130

East Asian (EAS) AF: 0.00520 AC: 14 AN: 2694

South Asian (SAS) AF: 0.0702 AC: 269 AN: 3834

European-Finnish (FIN) AF: 0.0323 AC: 50 AN: 1546

Middle Eastern (MID) AF: 0.0287 AC: 5 AN: 174

European-Non Finnish (NFE) AF: 0.0283 AC: 781 AN: 27586

Other (OTH) AF: 0.0394 AC: 100 AN: 2538

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

African (AFR) AF: 0.107 AC: 4429 AN: 41540

American (AMR) AF: 0.0265 AC: 405 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.100 AC: 348 AN: 3468

East Asian (EAS) AF: 0.00851 AC: 44 AN: 5168

South Asian (SAS) AF: 0.0763 AC: 368 AN: 4820

European-Finnish (FIN) AF: 0.0461 AC: 490 AN: 10618

Middle Eastern (MID) AF: 0.0479 AC: 14 AN: 292

European-Non Finnish (NFE) AF: 0.0308 AC: 2096 AN: 68012

Other (OTH) AF: 0.0545 AC: 115 AN: 2110

Alfa AF: 0.0388 Hom.: 191

Bravo AF: 0.0540

Asia WGS AF: 0.0550 AC: 189 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.73
DANN	Benign	0.53
PhyloP100		-1.0
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: rs11823728; hg19: chr11-62676802;