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. Variant got -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

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:58194):

LOC124902683 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHRM1	NM_000738.3	c.-79+3460G>T		intron_variant	Intron 1 of 1	ENST00000306960.4	NP_000729.2
CHRM1	XM_011544742.3	c.-79+4080G>T		intron_variant	Intron 1 of 1		XP_011543044.1
LOC124902683	XR_007062700.1	n.330-168C>A		intron_variant	Intron 2 of 2
LOC124902683	XR_007062701.1	n.330-165C>A		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHRM1	ENST00000306960.4	c.-79+3460G>T		intron_variant	Intron 1 of 1	1	NM_000738.3	ENSP00000306490.3
CHRM1	ENST00000543973.1	c.-79+2915G>T		intron_variant	Intron 2 of 2	5		ENSP00000441188.1
ENSG00000257002	ENST00000543624.1	n.314-168C>A		intron_variant	Intron 2 of 2	3

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

Gnomad4 AFR AF: 0.834

Gnomad4 AMR AF: 0.773

Gnomad4 ASJ AF: 0.777

Gnomad4 EAS AF: 0.859

Gnomad4 SAS AF: 0.794

Gnomad4 FIN AF: 0.773

Gnomad4 NFE AF: 0.706

Gnomad4 OTH AF: 0.734

Alfa AF: 0.719 Hom.: 79852

Bravo AF: 0.765

Asia WGS AF: 0.820 AC: 2851 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	6.6
DANN	Benign	0.53

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: rs544978; hg19: chr11-62685230;