rs2067480

Variant names:

• chr11-62909748-G-A
• rs2067480
• NM_000738.3:c.1353C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_000738.3(CHRM1):​c.1353C>T​(p.Ser451Ser) 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 1,614,016 control chromosomes in the GnomAD database, including 8,408 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 (940 hom., cov: 33)
  • Exomes 𝑓: 0.092 (7468 hom.)
• Consequence: CHRM1 NM_000738.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.851

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]

ENSG00000257002 (HGNC:58194):

LOC124902683 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP7: Synonymous conserved (PhyloP=-0.851 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 rank	MANE	Protein	UniProt
CHRM1	NM_000738.3	c.1353C>T	p.Ser451Ser	synonymous_variant	Exon 2 of 2	ENST00000306960.4	NP_000729.2
CHRM1	XM_011544742.3	c.1353C>T	p.Ser451Ser	synonymous_variant	Exon 2 of 2		XP_011543044.1
LOC124902683	XR_007062700.1	n.86+133G>A		intron_variant	Intron 1 of 2
LOC124902683	XR_007062701.1	n.86+133G>A		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHRM1	ENST00000306960.4	c.1353C>T	p.Ser451Ser	synonymous_variant	Exon 2 of 2	1	NM_000738.3	ENSP00000306490.3
CHRM1	ENST00000543973.1	c.1353C>T	p.Ser451Ser	synonymous_variant	Exon 3 of 3	5		ENSP00000441188.1
ENSG00000257002	ENST00000543624.1	n.70+133G>A		intron_variant	Intron 1 of 2	3

Frequencies

GnomAD3 genomes AF: 0.0882 AC: 13421 AN: 152222 Hom.: 938 Cov.: 33

Gnomad AFR AF: 0.0202

Gnomad AMI AF: 0.144

Gnomad AMR AF: 0.232

Gnomad ASJ AF: 0.0904

Gnomad EAS AF: 0.0898

Gnomad SAS AF: 0.0347

Gnomad FIN AF: 0.146

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.0909

Gnomad OTH AF: 0.0889

GnomAD2 exomes AF: 0.111 AC: 27895 AN: 250728 AF XY: 0.104

Gnomad AFR exome AF: 0.0193

Gnomad AMR exome AF: 0.273

Gnomad ASJ exome AF: 0.0881

Gnomad EAS exome AF: 0.0937

Gnomad FIN exome AF: 0.148

Gnomad NFE exome AF: 0.0926

Gnomad OTH exome AF: 0.114

GnomAD4 exome AF: 0.0917 AC: 134091 AN: 1461676 Hom.: 7468 Cov.: 32 AF XY: 0.0902 AC XY: 65619 AN XY: 727122

Gnomad4 AFR exome AF: 0.0178 AC: 596 AN: 33480

Gnomad4 AMR exome AF: 0.272 AC: 12155 AN: 44722

Gnomad4 ASJ exome AF: 0.0901 AC: 2355 AN: 26136

Gnomad4 EAS exome AF: 0.0814 AC: 3232 AN: 39700

Gnomad4 SAS exome AF: 0.0377 AC: 3256 AN: 86252

Gnomad4 FIN exome AF: 0.141 AC: 7540 AN: 53372

Gnomad4 NFE exome AF: 0.0893 AC: 99263 AN: 1111866

Gnomad4 Remaining exome AF: 0.0849 AC: 5129 AN: 60380

GnomAD4 genome AF: 0.0882 AC: 13438 AN: 152340 Hom.: 940 Cov.: 33 AF XY: 0.0940 AC XY: 7002 AN XY: 74492

Gnomad4 AFR AF: 0.0201 AC: 0.0201491 AN: 0.0201491

Gnomad4 AMR AF: 0.232 AC: 0.232283 AN: 0.232283

Gnomad4 ASJ AF: 0.0904 AC: 0.0904378 AN: 0.0904378

Gnomad4 EAS AF: 0.0904 AC: 0.0904173 AN: 0.0904173

Gnomad4 SAS AF: 0.0345 AC: 0.034547 AN: 0.034547

Gnomad4 FIN AF: 0.146 AC: 0.146112 AN: 0.146112

Gnomad4 NFE AF: 0.0909 AC: 0.0909011 AN: 0.0909011

Gnomad4 OTH AF: 0.0918 AC: 0.0917692 AN: 0.0917692

Alfa AF: 0.0850 Hom.: 275

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	-0.82
CADD	Benign	1.0
DANN	Benign	0.90
Mutation Taster		=99/1	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

Publications

LitVar

Other links and lift over

dbSNP: rs2067480; hg19: chr11-62677220; COSMIC: COSV61006307; COSMIC: COSV61006307;