rs2067479

Positions:

• chr11-62909880-G-A
• chr11-62909880-G-C

Variant summary

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

The NM_000738.3(CHRM1):​c.1221C>T​(p.Cys407=) variant causes a synonymous change. The variant allele was found at a frequency of 0.0527 in 1,614,200 control chromosomes in the GnomAD database, including 2,624 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 0.040 (167 hom., cov: 32)
  • Exomes 𝑓: 0.054 (2457 hom.)
• Consequence: CHRM1 NM_000738.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.79

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0588 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHRM1	NM_000738.3	c.1221C>T	p.Cys407=	synonymous_variant	2/2	ENST00000306960.4
LOC124902683	XR_007062701.1	n.86+265G>A		intron_variant, non_coding_transcript_variant
CHRM1	XM_011544742.3	c.1221C>T	p.Cys407=	synonymous_variant	2/2
LOC124902683	XR_007062700.1	n.86+265G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHRM1	ENST00000306960.4	c.1221C>T	p.Cys407=	synonymous_variant	2/2	1	NM_000738.3	P1
	ENST00000543624.1	n.70+265G>A		intron_variant, non_coding_transcript_variant		3
CHRM1	ENST00000543973.1	c.1221C>T	p.Cys407=	synonymous_variant	3/3	5

Frequencies

GnomAD3 genomes AF: 0.0398 AC: 6053 AN: 152200 Hom.: 167 Cov.: 32

Gnomad AFR AF: 0.0110

Gnomad AMI AF: 0.0263

Gnomad AMR AF: 0.0370

Gnomad ASJ AF: 0.0325

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0418

Gnomad FIN AF: 0.0446

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0603

Gnomad OTH AF: 0.0440

GnomAD3 exomes AF: 0.0410 AC: 10311 AN: 251430 Hom.: 283 AF XY: 0.0421 AC XY: 5716 AN XY: 135896

Gnomad AFR exome AF: 0.0106

Gnomad AMR exome AF: 0.0241

Gnomad ASJ exome AF: 0.0285

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.0422

Gnomad FIN exome AF: 0.0448

Gnomad NFE exome AF: 0.0572

Gnomad OTH exome AF: 0.0417

GnomAD4 exome AF: 0.0541 AC: 79075 AN: 1461882 Hom.: 2457 Cov.: 33 AF XY: 0.0537 AC XY: 39042 AN XY: 727246

Gnomad4 AFR exome AF: 0.00899

Gnomad4 AMR exome AF: 0.0250

Gnomad4 ASJ exome AF: 0.0316

Gnomad4 EAS exome AF: 0.000126

Gnomad4 SAS exome AF: 0.0411

Gnomad4 FIN exome AF: 0.0462

Gnomad4 NFE exome AF: 0.0611

Gnomad4 OTH exome AF: 0.0442

GnomAD4 genome AF: 0.0397 AC: 6048 AN: 152318 Hom.: 167 Cov.: 32 AF XY: 0.0393 AC XY: 2924 AN XY: 74490

Gnomad4 AFR AF: 0.0109

Gnomad4 AMR AF: 0.0369

Gnomad4 ASJ AF: 0.0325

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.0421

Gnomad4 FIN AF: 0.0446

Gnomad4 NFE AF: 0.0603

Gnomad4 OTH AF: 0.0430

Alfa AF: 0.0522 Hom.: 437

Bravo AF: 0.0366

Asia WGS AF: 0.0140 AC: 51 AN: 3478

EpiCase AF: 0.0599

EpiControl AF: 0.0574

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	9.3
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: rs2067479; hg19: chr11-62677352;