dbSNP rs499167: CHRM5:c.-75-6506A>C (chr15-34056137-A-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_012125.4(CHRM5):c.-75-6506A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.651 in 152,040 control chromosomes in the GnomAD database, including 33,462 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 0.65 ( 33462 hom., cov: 32)

Consequence

CHRM5
NM_012125.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.505

Publications

2 publications found

Variant links:

Genes affected

CHRM5 (HGNC:1954): (cholinergic receptor muscarinic 5) 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 clinical implications of this receptor are unknown; however, stimulation of this receptor is known to increase cyclic AMP levels. [provided by RefSeq, Jul 2008]

CHRM5 links:

AVEN (HGNC:13509): (apoptosis and caspase activation inhibitor) Involved in negative regulation of apoptotic process. Located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

AVEN 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=-0.92).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.755 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012125.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHRM5	NM_012125.4	MANE Select	c.-75-6506A>C		intron	N/A	NP_036257.1
	CHRM5	NM_001320917.2		c.-75-6506A>C		intron	N/A	NP_001307846.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
CHRM5	ENST00000383263.7	TSL:2 MANE Select	c.-75-6506A>C	intron	N/A	ENSP00000372750.5
CHRM5	ENST00000557872.1	TSL:1	c.-75-6506A>C	intron	N/A	ENSP00000453745.1
CHRM5	ENST00000560035.1	TSL:4	c.-75-6506A>C	intron	N/A	ENSP00000452742.1

Frequencies

GnomAD3 genomes

AF:

0.651

AC:

98959

AN:

151922

Hom.:

33455

Cov.:

show subpopulations

Gnomad AFR

AF:

0.468

Gnomad AMI

AF:

0.788

Gnomad AMR

AF:

0.652

Gnomad ASJ

AF:

0.559

Gnomad EAS

AF:

0.653

Gnomad SAS

AF:

0.776

Gnomad FIN

AF:

0.675

Gnomad MID

AF:

0.620

Gnomad NFE

AF:

0.753

Gnomad OTH

AF:

0.663

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.651

AC:

99006

AN:

152040

Hom.:

33462

Cov.:

AF XY:

0.649

AC XY:

48231

AN XY:

74324

show subpopulations

African (AFR)

AF:

0.468

AC:

19417

AN:

41462

American (AMR)

AF:

0.652

AC:

9952

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.559

AC:

1941

AN:

3470

East Asian (EAS)

AF:

0.652

AC:

3357

AN:

5146

South Asian (SAS)

AF:

0.776

AC:

3745

AN:

4826

European-Finnish (FIN)

AF:

0.675

AC:

7127

AN:

10560

Middle Eastern (MID)

AF:

0.619

AC:

182

AN:

294

European-Non Finnish (NFE)

AF:

0.753

AC:

51162

AN:

67988

Other (OTH)

AF:

0.665

AC:

1406

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1685

3370

5055

6740

8425

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

802

1604

2406

3208

4010

<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:

0.713

Hom.:

14745

Bravo

AF:

0.638

Asia WGS

AF:

0.724

AC:

2520

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

1.4

(source)

DANN

Benign

0.63

PhyloP100

-0.51

Mutation Taster

=100/0

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over