Genetic Variant NM_012125.4:c.-407-24438C>T (chr15-34022102-C-T) – 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.-407-24438C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.627 in 152,124 control chromosomes in the GnomAD database, including 34,901 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 0.63 ( 34901 hom., cov: 32)

Consequence

CHRM5
NM_012125.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.610

Publications

1 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:

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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=-0.82).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.818 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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
CHRM5	NM_012125.4	MANE Select	c.-407-24438C>T	intron	N/A	NP_036257.1
AVEN	NM_020371.3	MANE Select	c.267+16678G>A	intron	N/A	NP_065104.1
CHRM5	NM_001320917.2		c.-75-40541C>T	intron	N/A	NP_001307846.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
CHRM5	ENST00000383263.7	TSL:2 MANE Select	c.-407-24438C>T	intron	N/A	ENSP00000372750.5
AVEN	ENST00000306730.8	TSL:1 MANE Select	c.267+16678G>A	intron	N/A	ENSP00000306822.3
CHRM5	ENST00000557872.1	TSL:1	c.-76+3637C>T	intron	N/A	ENSP00000453745.1

Frequencies

GnomAD3 genomes

AF:

0.627

AC:

95332

AN:

152006

Hom.:

34906

Cov.:

show subpopulations

Gnomad AFR

AF:

0.230

Gnomad AMI

AF:

0.745

Gnomad AMR

AF:

0.712

Gnomad ASJ

AF:

0.834

Gnomad EAS

AF:

0.501

Gnomad SAS

AF:

0.618

Gnomad FIN

AF:

0.768

Gnomad MID

AF:

0.707

Gnomad NFE

AF:

0.824

Gnomad OTH

AF:

0.697

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

GnomAD4 genome

AF:

0.627

AC:

95345

AN:

152124

Hom.:

34901

Cov.:

AF XY:

0.625

AC XY:

46450

AN XY:

74350

show subpopulations

African (AFR)

AF:

0.230

AC:

9528

AN:

41498

American (AMR)

AF:

0.712

AC:

10878

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.834

AC:

2894

AN:

3468

East Asian (EAS)

AF:

0.501

AC:

2590

AN:

5174

South Asian (SAS)

AF:

0.618

AC:

2979

AN:

4818

European-Finnish (FIN)

AF:

0.768

AC:

8111

AN:

10568

Middle Eastern (MID)

AF:

0.709

AC:

207

AN:

292

European-Non Finnish (NFE)

AF:

0.824

AC:

56010

AN:

67994

Other (OTH)

AF:

0.696

AC:

1469

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1353

2706

4058

5411

6764

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

730

1460

2190

2920

3650

<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:

0.767

Hom.:

23258

Bravo

AF:

0.605

Asia WGS

AF:

0.570

AC:

1981

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

4.7

(source)

DANN

Benign

0.42

PhyloP100

0.61

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