rs2067479

Variant names:

• chr11-62909880-G-A
• rs2067479
• NM_000738.3:c.1221C>T

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000738.3(CHRM1):​c.1221C>T​(p.Cys407Cys) 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
• Publications: 7 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=-0.49).
• 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 rank	MANE	Protein	UniProt
CHRM1	NM_000738.3	c.1221C>T	p.Cys407Cys	synonymous_variant	Exon 2 of 2	ENST00000306960.4	NP_000729.2
CHRM1	XM_011544742.3	c.1221C>T	p.Cys407Cys	synonymous_variant	Exon 2 of 2		XP_011543044.1
CHRM1-AS1	NR_199052.1	n.209+265G>A		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHRM1	ENST00000306960.4	c.1221C>T	p.Cys407Cys	synonymous_variant	Exon 2 of 2	1	NM_000738.3	ENSP00000306490.3

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

GnomAD2 exomes AF: 0.0410 AC: 10311 AN: 251430 AF XY: 0.0421

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 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

African (AFR) AF: 0.00899 AC: 301 AN: 33480

American (AMR) AF: 0.0250 AC: 1118 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0316 AC: 827 AN: 26136

East Asian (EAS) AF: 0.000126 AC: 5 AN: 39700

South Asian (SAS) AF: 0.0411 AC: 3544 AN: 86258

European-Finnish (FIN) AF: 0.0462 AC: 2466 AN: 53416

Middle Eastern (MID) AF: 0.0352 AC: 203 AN: 5768

European-Non Finnish (NFE) AF: 0.0611 AC: 67942 AN: 1112004

Other (OTH) AF: 0.0442 AC: 2669 AN: 60396

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

African (AFR) AF: 0.0109 AC: 454 AN: 41578

American (AMR) AF: 0.0369 AC: 565 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0325 AC: 113 AN: 3472

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5182

South Asian (SAS) AF: 0.0421 AC: 203 AN: 4826

European-Finnish (FIN) AF: 0.0446 AC: 473 AN: 10616

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.0603 AC: 4103 AN: 68020

Other (OTH) AF: 0.0430 AC: 91 AN: 2114

Alfa AF: 0.0498 Hom.: 564

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
PhyloP100		5.8
Mutation Taster		=96/4	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: rs2067479; hg19: chr11-62677352;