rs2067478

chr11-62910057-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_000738.3(CHRM1):c.1044G>A(p.Gln348=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0373 in 1,613,392 control chromosomes in the GnomAD database, including 1,568 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 0.056 (311 hom., cov: 32)
  • Exomes 𝑓: 0.035 (1257 hom.)
• Consequence: CHRM1 NM_000738.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.158

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BP7: Synonymous conserved (PhyloP=0.158 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.107 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHRM1	NM_000738.3	c.1044G>A	p.Gln348=	synonymous_variant	2/2	ENST00000306960.4
LOC124902683	XR_007062701.1	n.86+442C>T		intron_variant, non_coding_transcript_variant
CHRM1	XM_011544742.3	c.1044G>A	p.Gln348=	synonymous_variant	2/2
LOC124902683	XR_007062700.1	n.86+442C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHRM1	ENST00000306960.4	c.1044G>A	p.Gln348=	synonymous_variant	2/2	1	NM_000738.3	P1
	ENST00000543624.1	n.70+442C>T		intron_variant, non_coding_transcript_variant		3
CHRM1	ENST00000543973.1	c.1044G>A	p.Gln348=	synonymous_variant	3/3	5

Frequencies

GnomAD3 genomes AF: 0.0555 AC: 8437 AN: 152132 Hom.: 308 Cov.: 32

Gnomad AFR AF: 0.109

Gnomad AMI AF: 0.0362

Gnomad AMR AF: 0.0263

Gnomad ASJ AF: 0.101

Gnomad EAS AF: 0.00829

Gnomad SAS AF: 0.0765

Gnomad FIN AF: 0.0461

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0308

Gnomad OTH AF: 0.0532

GnomAD3 exomes AF: 0.0404 AC: 10106 AN: 250414 Hom.: 306 AF XY: 0.0419 AC XY: 5675 AN XY: 135380

Gnomad AFR exome AF: 0.111

Gnomad AMR exome AF: 0.0138

Gnomad ASJ exome AF: 0.107

Gnomad EAS exome AF: 0.00843

Gnomad SAS exome AF: 0.0625

Gnomad FIN exome AF: 0.0459

Gnomad NFE exome AF: 0.0302

Gnomad OTH exome AF: 0.0469

GnomAD4 exome AF: 0.0353 AC: 51635 AN: 1461142 Hom.: 1257 Cov.: 33 AF XY: 0.0364 AC XY: 26466 AN XY: 726884

Gnomad4 AFR exome AF: 0.112

Gnomad4 AMR exome AF: 0.0143

Gnomad4 ASJ exome AF: 0.106

Gnomad4 EAS exome AF: 0.00423

Gnomad4 SAS exome AF: 0.0652

Gnomad4 FIN exome AF: 0.0427

Gnomad4 NFE exome AF: 0.0302

Gnomad4 OTH exome AF: 0.0426

GnomAD4 genome AF: 0.0556 AC: 8470 AN: 152250 Hom.: 311 Cov.: 32 AF XY: 0.0557 AC XY: 4144 AN XY: 74436

Gnomad4 AFR AF: 0.110

Gnomad4 AMR AF: 0.0263

Gnomad4 ASJ AF: 0.101

Gnomad4 EAS AF: 0.00850

Gnomad4 SAS AF: 0.0764

Gnomad4 FIN AF: 0.0461

Gnomad4 NFE AF: 0.0308

Gnomad4 OTH AF: 0.0550

Alfa AF: 0.0447 Hom.: 130

Bravo AF: 0.0550

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	-0.53
Cadd	Benign	5.5
Dann	Benign	0.88

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: rs2067478; hg19: chr11-62677529;