rs2186410

Positions:

• chr11-62917945-G-A

Variant summary

Our verdict is Benign. Variant got -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

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]

ENSG00000257002 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHRM1	NM_000738.3	c.-79+3273C>T		intron_variant		ENST00000306960.4	NP_000729.2
CHRM1	XM_011544742.3	c.-79+3893C>T		intron_variant			XP_011543044.1
LOC124902683	XR_007062700.1	n.349G>A		non_coding_transcript_exon_variant	3/3
LOC124902683	XR_007062701.1	n.352G>A		non_coding_transcript_exon_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHRM1	ENST00000306960.4	c.-79+3273C>T		intron_variant		1	NM_000738.3	ENSP00000306490.3
CHRM1	ENST00000543973.1	c.-79+2728C>T		intron_variant		5		ENSP00000441188.1
ENSG00000257002	ENST00000543624.1	n.333G>A		non_coding_transcript_exon_variant	3/3	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

Gnomad4 ASJ exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

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

Gnomad4 AFR AF: 0.0238

Gnomad4 AMR AF: 0.263

Gnomad4 ASJ AF: 0.0900

Gnomad4 EAS AF: 0.0910

Gnomad4 SAS AF: 0.0335

Gnomad4 FIN AF: 0.145

Gnomad4 NFE AF: 0.0909

Gnomad4 OTH AF: 0.0932

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	7.5
DANN	Benign	0.72

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: rs2186410; hg19: chr11-62685417;