rs2067477

chr11-62910834-G-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_000738.3(CHRM1):c.267C>A(p.Gly89=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0914 in 1,614,004 control chromosomes in the GnomAD database, including 8,404 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 0.088 (935 hom., cov: 32)
  • Exomes 𝑓: 0.092 (7469 hom.)
• Consequence: CHRM1 NM_000738.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.40

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• BP7: Synonymous conserved (PhyloP=3.4 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.226 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHRM1	NM_000738.3	c.267C>A	p.Gly89=	synonymous_variant	2/2	ENST00000306960.4
LOC124902683	XR_007062701.1	n.318G>T		non_coding_transcript_exon_variant	2/3
CHRM1	XM_011544742.3	c.267C>A	p.Gly89=	synonymous_variant	2/2
LOC124902683	XR_007062700.1	n.318G>T		non_coding_transcript_exon_variant	2/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHRM1	ENST00000306960.4	c.267C>A	p.Gly89=	synonymous_variant	2/2	1	NM_000738.3	P1
	ENST00000543624.1	n.302G>T		non_coding_transcript_exon_variant	2/3	3
CHRM1	ENST00000543973.1	c.267C>A	p.Gly89=	synonymous_variant	3/3	5
CHRM1	ENST00000536524.1	c.267C>A	p.Gly89=	synonymous_variant	2/2	4

Frequencies

GnomAD3 genomes AF: 0.0881 AC: 13399 AN: 152054 Hom.: 933 Cov.: 32

Gnomad AFR AF: 0.0199

Gnomad AMI AF: 0.144

Gnomad AMR AF: 0.232

Gnomad ASJ AF: 0.0902

Gnomad EAS AF: 0.0905

Gnomad SAS AF: 0.0344

Gnomad FIN AF: 0.145

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.0910

Gnomad OTH AF: 0.0887

GnomAD3 exomes AF: 0.111 AC: 27945 AN: 251330 Hom.: 2319 AF XY: 0.104 AC XY: 14063 AN XY: 135854

Gnomad AFR exome AF: 0.0192

Gnomad AMR exome AF: 0.273

Gnomad ASJ exome AF: 0.0876

Gnomad EAS exome AF: 0.0947

Gnomad SAS exome AF: 0.0376

Gnomad FIN exome AF: 0.148

Gnomad NFE exome AF: 0.0926

Gnomad OTH exome AF: 0.114

GnomAD4 exome AF: 0.0917 AC: 134109 AN: 1461832 Hom.: 7469 Cov.: 33 AF XY: 0.0902 AC XY: 65623 AN XY: 727222

Gnomad4 AFR exome AF: 0.0178

Gnomad4 AMR exome AF: 0.272

Gnomad4 ASJ exome AF: 0.0896

Gnomad4 EAS exome AF: 0.0818

Gnomad4 SAS exome AF: 0.0377

Gnomad4 FIN exome AF: 0.141

Gnomad4 NFE exome AF: 0.0893

Gnomad4 OTH exome AF: 0.0850

GnomAD4 genome AF: 0.0882 AC: 13416 AN: 152172 Hom.: 935 Cov.: 32 AF XY: 0.0939 AC XY: 6988 AN XY: 74408

Gnomad4 AFR AF: 0.0199

Gnomad4 AMR AF: 0.232

Gnomad4 ASJ AF: 0.0902

Gnomad4 EAS AF: 0.0911

Gnomad4 SAS AF: 0.0342

Gnomad4 FIN AF: 0.145

Gnomad4 NFE AF: 0.0910

Gnomad4 OTH AF: 0.0916

Alfa AF: 0.0890 Hom.: 1105

Bravo AF: 0.0930

Asia WGS AF: 0.0690 AC: 240 AN: 3478

EpiCase AF: 0.0884

EpiControl AF: 0.0818

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
Cadd	Benign	16
Dann	Benign	0.89

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: rs2067477; hg19: chr11-62678306; COSMIC: COSV61006161;