Variant rs2067478 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_000738.3(CHRM1):c.1044G>A(p.Gln348Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0373 in 1,613,392 control chromosomes in the GnomAD database, including 1,568 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 0.056 ( 311 hom., cov: 32)

Exomes 𝑓: 0.035 ( 1257 hom. )

Consequence

CHRM1
NM_000738.3 synonymous

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:):

ENSG00000257002 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.53).

BP7

Synonymous conserved (PhyloP=0.158 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.107 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHRM1	NM_000738.3 linkuse as main transcript	c.1044G>A	p.Gln348Gln	synonymous_variant	2/2	ENST00000306960.4	NP_000729.2	P11229-1Q53XZ3
CHRM1	XM_011544742.3 linkuse as main transcript	c.1044G>A	p.Gln348Gln	synonymous_variant	2/2		XP_011543044.1	P11229-1Q53XZ3
LOC124902683	XR_007062700.1 linkuse as main transcript	n.86+442C>T		intron_variant
LOC124902683	XR_007062701.1 linkuse as main transcript	n.86+442C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CHRM1	ENST00000306960.4 linkuse as main transcript	c.1044G>A	p.Gln348Gln	synonymous_variant	2/2	1	NM_000738.3	ENSP00000306490.3	P11229-1
CHRM1	ENST00000543973.1 linkuse as main transcript	c.1044G>A	p.Gln348Gln	synonymous_variant	3/3	5		ENSP00000441188.1	P11229-2
ENSG00000257002	ENST00000543624.1 linkuse as main transcript	n.70+442C>T		intron_variant		3

Frequencies

GnomAD3 genomes

AF:

0.0555

AC:

8437

AN:

152132

Hom.:

308

Cov.:

show subpopulations

Gnomad AFR

AF:

0.109

Gnomad AMI

AF:

0.0362

Gnomad AMR

AF:

0.0263

Gnomad ASJ

AF:

0.101

Gnomad EAS

AF:

0.00829

Gnomad SAS

AF:

0.0765

Gnomad FIN

AF:

0.0461

Gnomad MID

AF:

0.0443

Gnomad NFE

AF:

0.0308

Gnomad OTH

AF:

0.0532

GnomAD3 exomes

AF:

0.0404

AC:

10106

AN:

250414

Hom.:

306

AF XY:

0.0419

AC XY:

5675

AN XY:

135380

show subpopulations

Gnomad AFR exome

AF:

0.111

Gnomad AMR exome

AF:

0.0138

Gnomad ASJ exome

AF:

0.107

Gnomad EAS exome

AF:

0.00843

Gnomad SAS exome

AF:

0.0625

Gnomad FIN exome

AF:

0.0459

Gnomad NFE exome

AF:

0.0302

Gnomad OTH exome

AF:

0.0469

GnomAD4 exome

AF:

0.0353

AC:

51635

AN:

1461142

Hom.:

1257

Cov.:

AF XY:

0.0364

AC XY:

26466

AN XY:

726884

show subpopulations

Gnomad4 AFR exome

AF:

0.112

Gnomad4 AMR exome

AF:

0.0143

Gnomad4 ASJ exome

AF:

0.106

Gnomad4 EAS exome

AF:

0.00423

Gnomad4 SAS exome

AF:

0.0652

Gnomad4 FIN exome

AF:

0.0427

Gnomad4 NFE exome

AF:

0.0302

Gnomad4 OTH exome

AF:

0.0426

GnomAD4 genome

AF:

0.0556

AC:

8470

AN:

152250

Hom.:

311

Cov.:

AF XY:

0.0557

AC XY:

4144

AN XY:

74436

show subpopulations

Gnomad4 AFR

AF:

0.110

Gnomad4 AMR

AF:

0.0263

Gnomad4 ASJ

AF:

0.101

Gnomad4 EAS

AF:

0.00850

Gnomad4 SAS

AF:

0.0764

Gnomad4 FIN

AF:

0.0461

Gnomad4 NFE

AF:

0.0308

Gnomad4 OTH

AF:

0.0550

Alfa

AF:

0.0447

Hom.:

130

Bravo

AF:

0.0550

Asia WGS

AF:

0.0550

AC:

189

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.53

CADD

Benign

5.5

DANN

Benign

0.88

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over