11-62910057-C-T

Variant names:

• chr11-62910057-C-T
• rs2067478
• NM_000738.3:c.1044G>A

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.1044G>A​(p.Gln348Gln) 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
• Publications: 5 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

CHRM1-AS1 (HGNC:58194):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000738.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHRM1	NM_000738.3	MANE Select	c.1044G>A	p.Gln348Gln	synonymous	Exon 2 of 2	NP_000729.2
	CHRM1-AS1	NR_199052.1		n.209+442C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHRM1	ENST00000306960.4	TSL:1 MANE Select	c.1044G>A	p.Gln348Gln	synonymous	Exon 2 of 2	ENSP00000306490.3	P11229-1
	CHRM1	ENST00000856787.1		c.1044G>A	p.Gln348Gln	synonymous	Exon 2 of 2	ENSP00000526846.1
	CHRM1	ENST00000856788.1		c.1044G>A	p.Gln348Gln	synonymous	Exon 3 of 3	ENSP00000526847.1

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

GnomAD2 exomes AF: 0.0404 AC: 10106 AN: 250414 AF XY: 0.0419

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 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

African (AFR) AF: 0.112 AC: 3744 AN: 33480

American (AMR) AF: 0.0143 AC: 640 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.106 AC: 2769 AN: 26108

East Asian (EAS) AF: 0.00423 AC: 168 AN: 39700

South Asian (SAS) AF: 0.0652 AC: 5626 AN: 86242

European-Finnish (FIN) AF: 0.0427 AC: 2255 AN: 52846

Middle Eastern (MID) AF: 0.0577 AC: 333 AN: 5768

European-Non Finnish (NFE) AF: 0.0302 AC: 33527 AN: 1111900

Other (OTH) AF: 0.0426 AC: 2573 AN: 60378

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

African (AFR) AF: 0.110 AC: 4559 AN: 41536

American (AMR) AF: 0.0263 AC: 402 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.101 AC: 349 AN: 3472

East Asian (EAS) AF: 0.00850 AC: 44 AN: 5176

South Asian (SAS) AF: 0.0764 AC: 368 AN: 4818

European-Finnish (FIN) AF: 0.0461 AC: 489 AN: 10614

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.0308 AC: 2096 AN: 68010

Other (OTH) AF: 0.0550 AC: 116 AN: 2110

Alfa AF: 0.0370 Hom.: 286

Bravo AF: 0.0550

Asia WGS AF: 0.0550 AC: 189 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	5.5
DANN	Benign	0.88
PhyloP100		0.16
Mutation Taster		=100/0	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: rs2067478; hg19: chr11-62677529;