dbSNP rs636842: CHRM5:c.-408+7265T>G (chr15-33976415-T-G) – 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.-408+7265T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.276 in 152,168 control chromosomes in the GnomAD database, including 7,359 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 0.28 ( 7359 hom., cov: 33)

Consequence

CHRM5
NM_012125.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.617

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=-0.88).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.383 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHRM5	NM_012125.4 link	c.-408+7265T>G		intron_variant	Intron 1 of 2	ENST00000383263.7	NP_036257.1	P08912A0A024R9I2Q8IVW0
AVEN	NM_020371.3 link	c.445+26617A>C		intron_variant	Intron 2 of 5	ENST00000306730.8	NP_065104.1	Q9NQS1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
CHRM5	ENST00000383263.7 link	c.-408+7265T>G	intron_variant	Intron 1 of 2	2	NM_012125.4	ENSP00000372750.5	P08912
AVEN	ENST00000306730.8 link	c.445+26617A>C	intron_variant	Intron 2 of 5	1	NM_020371.3	ENSP00000306822.3	Q9NQS1
CHRM5	ENST00000560035.1 link	c.-76+7265T>G	intron_variant	Intron 1 of 1	4		ENSP00000452742.1	H0YKC0
AVEN	ENST00000675287.1 link	n.1815+26617A>C	intron_variant	Intron 6 of 11

Frequencies

GnomAD3 genomes

AF:

0.276

AC:

41943

AN:

152052

Hom.:

7359

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0718

Gnomad AMI

AF:

0.327

Gnomad AMR

AF:

0.361

Gnomad ASJ

AF:

0.361

Gnomad EAS

AF:

0.119

Gnomad SAS

AF:

0.235

Gnomad FIN

AF:

0.297

Gnomad MID

AF:

0.288

Gnomad NFE

AF:

0.387

Gnomad OTH

AF:

0.301

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

GnomAD4 genome

AF:

0.276

AC:

41947

AN:

152168

Hom.:

7359

Cov.:

AF XY:

0.269

AC XY:

20026

AN XY:

74396

show subpopulations

African (AFR)

AF:

0.0716

AC:

2974

AN:

41556

American (AMR)

AF:

0.362

AC:

5523

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.361

AC:

1252

AN:

3468

East Asian (EAS)

AF:

0.119

AC:

617

AN:

5188

South Asian (SAS)

AF:

0.236

AC:

1136

AN:

4820

European-Finnish (FIN)

AF:

0.297

AC:

3140

AN:

10580

Middle Eastern (MID)

AF:

0.289

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.387

AC:

26294

AN:

67970

Other (OTH)

AF:

0.298

AC:

628

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1446

2891

4337

5782

7228

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

422

844

1266

1688

2110

<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:

0.323

Hom.:

10212

Bravo

AF:

0.271

Asia WGS

AF:

0.189

AC:

655

AN:

3462

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

8.8

(source)

DANN

Benign

0.70

PhyloP100

-0.62

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over