rs2186410

Variant names:

• chr11-62917945-G-A
• rs2186410
• NM_000738.3:c.-79+3273C>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+3273C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0922 in 152,040 control chromosomes in the GnomAD database, including 1,071 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 0.092 (1071 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CHRM1 NM_000738.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.840
• Publications: 2 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=-0.81).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.256 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+3273C>T		intron	N/A	NP_000729.2
	CHRM1-AS1	NR_199052.1		n.472G>A		non_coding_transcript_exon	Exon 3 of 3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHRM1	ENST00000306960.4	TSL:1 MANE Select	c.-79+3273C>T		intron	N/A	ENSP00000306490.3
	ENSG00000257002	ENST00000543624.2	TSL:3	n.425G>A		non_coding_transcript_exon	Exon 3 of 3
	ENSG00000257002	ENST00000782435.1		n.717G>A		non_coding_transcript_exon	Exon 3 of 3

Frequencies

GnomAD3 genomes AF: 0.0921 AC: 13996 AN: 151922 Hom.: 1068 Cov.: 32

Gnomad AFR AF: 0.0236

Gnomad AMI AF: 0.148

Gnomad AMR AF: 0.263

Gnomad ASJ AF: 0.0900

Gnomad EAS AF: 0.0904

Gnomad SAS AF: 0.0337

Gnomad FIN AF: 0.145

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.0909

Gnomad OTH AF: 0.0903

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 16 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 12

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 4

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 4

Other (OTH) AF: 0.00 AC: 0 AN: 4

GnomAD4 genome AF: 0.0922 AC: 14024 AN: 152040 Hom.: 1071 Cov.: 32 AF XY: 0.0984 AC XY: 7315 AN XY: 74302

African (AFR) AF: 0.0238 AC: 988 AN: 41476

American (AMR) AF: 0.263 AC: 4014 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.0900 AC: 312 AN: 3468

East Asian (EAS) AF: 0.0910 AC: 471 AN: 5174

South Asian (SAS) AF: 0.0335 AC: 161 AN: 4810

European-Finnish (FIN) AF: 0.145 AC: 1533 AN: 10560

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.0909 AC: 6177 AN: 67960

Other (OTH) AF: 0.0932 AC: 197 AN: 2114

Alfa AF: 0.0983 Hom.: 111

Bravo AF: 0.0996

Asia WGS AF: 0.0720 AC: 250 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	7.5
DANN	Benign	0.72
PhyloP100		0.84
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: rs2186410; hg19: chr11-62685417;