dbSNP rs2067478: CHRM1:p.Gln348His (chr11-62910057-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_000738.3(CHRM1):c.1044G>T(p.Gln348His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,150 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

CHRM1
NM_000738.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.158

Variant links:

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 links:

ENSG00000257002 (HGNC:58194):

ENSG00000257002 links:

LOC124902683 (HGNC:):

LOC124902683 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.1542243).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHRM1	NM_000738.3 link	c.1044G>T	p.Gln348His	missense_variant	Exon 2 of 2	ENST00000306960.4	NP_000729.2	P11229-1Q53XZ3
CHRM1	XM_011544742.3 link	c.1044G>T	p.Gln348His	missense_variant	Exon 2 of 2		XP_011543044.1	P11229-1Q53XZ3
LOC124902683	XR_007062700.1 link	n.86+442C>A		intron_variant	Intron 1 of 2
LOC124902683	XR_007062701.1 link	n.86+442C>A		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CHRM1	ENST00000306960.4 link	c.1044G>T	p.Gln348His	missense_variant	Exon 2 of 2	1	NM_000738.3	ENSP00000306490.3	P11229-1
CHRM1	ENST00000543973.1 link	c.1044G>T	p.Gln348His	missense_variant	Exon 3 of 3	5		ENSP00000441188.1	P11229-2
ENSG00000257002	ENST00000543624.1 link	n.70+442C>A		intron_variant	Intron 1 of 2	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461150

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726884

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.65

D;.

Eigen

Benign

-0.37

Eigen_PC

Benign

-0.25

FATHMM_MKL

Benign

0.74

LIST_S2

Benign

0.55

T;T

M_CAP

Benign

0.0044

MetaRNN

Benign

0.15

T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.56

N;N

PrimateAI

Uncertain

0.59

PROVEAN

Benign

-2.3

N;N

REVEL

Benign

0.047

Sift

Benign

0.032

D;D

Sift4G

Uncertain

0.059

T;.

Polyphen

0.0020

B;.

Vest4

0.23

MutPred

0.41

Loss of ubiquitination at K353 (P = 0.0957);Loss of ubiquitination at K353 (P = 0.0957);

MVP

0.70

MPC

1.4

ClinPred

0.26

GERP RS

1.5

Varity_R

0.11

gMVP

0.79

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over