rs544978

Variant names:

• chr11-62917758-C-A
• rs544978
• NM_000738.3:c.-79+3460G>T

Your query was ambiguous. Multiple possible variants found:

• chr11-62917758-C-A
• chr11-62917758-C-G
• chr11-62917758-C-T

Variant summary

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

The NM_000738.3(CHRM1):​c.-79+3460G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.763 in 152,068 control chromosomes in the GnomAD database, including 44,418 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 0.76 (44418 hom., cov: 31)
• Consequence: CHRM1 NM_000738.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.28
• Publications: 15 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.838 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHRM1	NM_000738.3	MANE Select	c.-79+3460G>T		intron	N/A	NP_000729.2
	CHRM1-AS1	NR_199052.1		n.453-168C>A		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHRM1	ENST00000306960.4	TSL:1 MANE Select	c.-79+3460G>T		intron	N/A	ENSP00000306490.3
	CHRM1	ENST00000543973.1	TSL:5	c.-79+2915G>T		intron	N/A	ENSP00000441188.1
	ENSG00000257002	ENST00000543624.2	TSL:3	n.406-168C>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.763 AC: 115890 AN: 151950 Hom.: 44379 Cov.: 31

Gnomad AFR AF: 0.834

Gnomad AMI AF: 0.757

Gnomad AMR AF: 0.773

Gnomad ASJ AF: 0.777

Gnomad EAS AF: 0.859

Gnomad SAS AF: 0.795

Gnomad FIN AF: 0.773

Gnomad MID AF: 0.756

Gnomad NFE AF: 0.706

Gnomad OTH AF: 0.733

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.763 AC: 115984 AN: 152068 Hom.: 44418 Cov.: 31 AF XY: 0.767 AC XY: 57034 AN XY: 74348

African (AFR) AF: 0.834 AC: 34607 AN: 41476

American (AMR) AF: 0.773 AC: 11809 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.777 AC: 2697 AN: 3470

East Asian (EAS) AF: 0.859 AC: 4455 AN: 5184

South Asian (SAS) AF: 0.794 AC: 3818 AN: 4810

European-Finnish (FIN) AF: 0.773 AC: 8177 AN: 10572

Middle Eastern (MID) AF: 0.748 AC: 220 AN: 294

European-Non Finnish (NFE) AF: 0.706 AC: 47960 AN: 67958

Other (OTH) AF: 0.734 AC: 1551 AN: 2112

Alfa AF: 0.723 Hom.: 170281

Bravo AF: 0.765

Asia WGS AF: 0.820 AC: 2851 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	6.6
DANN	Benign	0.53
PhyloP100		1.3
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: rs544978; hg19: chr11-62685230;