Genetic Variant NM_000738.3:c.1221C>T (chr11-62909880-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000738.3(CHRM1):c.1221C>T(p.Cys407Cys) variant causes a synonymous change. The variant allele was found at a frequency of 0.0527 in 1,614,200 control chromosomes in the GnomAD database, including 2,624 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 0.040 ( 167 hom., cov: 32)

Exomes 𝑓: 0.054 ( 2457 hom. )

Consequence

CHRM1
NM_000738.3 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.79

Publications

7 publications found

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 Gene-Disease associations (from GenCC):

intellectual disability
Inheritance: AD Classification: LIMITED Submitted by: G2P

CHRM1 links:

ENSG00000257002 (HGNC:58194):

ENSG00000257002 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.49).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0588 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHRM1	NM_000738.3 link	c.1221C>T	p.Cys407Cys	synonymous_variant	Exon 2 of 2	ENST00000306960.4	NP_000729.2	P11229-1Q53XZ3
CHRM1	XM_011544742.3 link	c.1221C>T	p.Cys407Cys	synonymous_variant	Exon 2 of 2		XP_011543044.1	P11229-1Q53XZ3
CHRM1-AS1	NR_199052.1 link	n.209+265G>A		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHRM1	ENST00000306960.4 link	c.1221C>T	p.Cys407Cys	synonymous_variant	Exon 2 of 2	1	NM_000738.3	ENSP00000306490.3		P11229-1

Frequencies

GnomAD3 genomes

AF:

0.0398

AC:

6053

AN:

152200

Hom.:

167

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0110

Gnomad AMI

AF:

0.0263

Gnomad AMR

AF:

0.0370

Gnomad ASJ

AF:

0.0325

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.0418

Gnomad FIN

AF:

0.0446

Gnomad MID

AF:

0.0728

Gnomad NFE

AF:

0.0603

Gnomad OTH

AF:

0.0440

GnomAD2 exomes

AF:

0.0410

AC:

10311

AN:

251430

AF XY:

0.0421

show subpopulations

Gnomad AFR exome

AF:

0.0106

Gnomad AMR exome

AF:

0.0241

Gnomad ASJ exome

AF:

0.0285

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.0448

Gnomad NFE exome

AF:

0.0572

Gnomad OTH exome

AF:

0.0417

GnomAD4 exome

AF:

0.0541

AC:

79075

AN:

1461882

Hom.:

2457

Cov.:

AF XY:

0.0537

AC XY:

39042

AN XY:

727246

show subpopulations

African (AFR)

AF:

0.00899

AC:

301

AN:

33480

American (AMR)

AF:

0.0250

AC:

1118

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0316

AC:

827

AN:

26136

East Asian (EAS)

AF:

0.000126

AC:

AN:

39700

South Asian (SAS)

AF:

0.0411

AC:

3544

AN:

86258

European-Finnish (FIN)

AF:

0.0462

AC:

2466

AN:

53416

Middle Eastern (MID)

AF:

0.0352

AC:

203

AN:

5768

European-Non Finnish (NFE)

AF:

0.0611

AC:

67942

AN:

1112004

Other (OTH)

AF:

0.0442

AC:

2669

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

5157

10314

15471

20628

25785

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2506

5012

7518

10024

12530

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0397

AC:

6048

AN:

152318

Hom.:

167

Cov.:

AF XY:

0.0393

AC XY:

2924

AN XY:

74490

show subpopulations

African (AFR)

AF:

0.0109

AC:

454

AN:

41578

American (AMR)

AF:

0.0369

AC:

565

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.0325

AC:

113

AN:

3472

East Asian (EAS)

AF:

0.000386

AC:

AN:

5182

South Asian (SAS)

AF:

0.0421

AC:

203

AN:

4826

European-Finnish (FIN)

AF:

0.0446

AC:

473

AN:

10616

Middle Eastern (MID)

AF:

0.0680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0603

AC:

4103

AN:

68020

Other (OTH)

AF:

0.0430

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

302

604

906

1208

1510

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

144

216

288

360

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0498

Hom.:

564

Bravo

AF:

0.0366

Asia WGS

AF:

0.0140

AC:

AN:

3478

EpiCase

AF:

0.0599

EpiControl

AF:

0.0574

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.49

CADD

Benign

9.3

(source)

DANN

Benign

0.89

PhyloP100

5.8

Mutation Taster

=96/4

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over