Genetic Variant AVEN:p.Gly47Ala (chr15-34038907-C-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_020371.3(AVEN):c.140G>C(p.Gly47Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000107 in 1,118,924 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00015 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00010 ( 0 hom. )

Consequence

AVEN
NM_020371.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.536

Publications

0 publications found

Variant links:

Genes affected

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:

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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.1213215).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020371.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
AVEN	NM_020371.3	MANE Select	c.140G>C	p.Gly47Ala	missense	Exon 1 of 6	NP_065104.1	Q9NQS1
CHRM5	NM_012125.4	MANE Select	c.-407-7633C>G		intron	N/A	NP_036257.1	P08912
CHRM5	NM_001320917.2		c.-75-23736C>G		intron	N/A	NP_001307846.1	P08912

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
AVEN	ENST00000306730.8	TSL:1 MANE Select	c.140G>C	p.Gly47Ala	missense	Exon 1 of 6	ENSP00000306822.3	Q9NQS1
CHRM5	ENST00000383263.7	TSL:2 MANE Select	c.-407-7633C>G		intron	N/A	ENSP00000372750.5	P08912
CHRM5	ENST00000557872.1	TSL:1	c.-76+20442C>G		intron	N/A	ENSP00000453745.1	P08912

Frequencies

GnomAD3 genomes

AF:

0.000149

AC:

AN:

147556

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00388

Gnomad SAS

AF:

0.000417

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00

AC:

AN:

1014

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000101

AC:

AN:

971260

Hom.:

Cov.:

AF XY:

0.0000825

AC XY:

AN XY:

460554

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

18582

American (AMR)

AF:

0.00

AC:

AN:

5026

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

9312

East Asian (EAS)

AF:

0.00705

AC:

AN:

13058

South Asian (SAS)

AF:

0.000157

AC:

AN:

19060

European-Finnish (FIN)

AF:

0.00

AC:

AN:

13826

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2302

European-Non Finnish (NFE)

AF:

0.00000117

AC:

AN:

854610

Other (OTH)

AF:

0.0000564

AC:

AN:

35484

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.453

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.000149

AC:

AN:

147664

Hom.:

Cov.:

AF XY:

0.000153

AC XY:

AN XY:

71970

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41074

American (AMR)

AF:

0.00

AC:

AN:

14874

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3374

East Asian (EAS)

AF:

0.00390

AC:

AN:

5134

South Asian (SAS)

AF:

0.000417

AC:

AN:

4796

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8998

Middle Eastern (MID)

AF:

0.00

AC:

AN:

288

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

66178

Other (OTH)

AF:

0.00

AC:

AN:

2046

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00

Hom.:

Bravo

AF:

0.0000945

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

0.0082

BayesDel_noAF

Benign

-0.23

CADD

Benign

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.029

Eigen

Benign

-0.031

Eigen_PC

Benign

-0.038

FATHMM_MKL

Benign

0.58

LIST_S2

Benign

0.24

M_CAP

Pathogenic

0.55

MetaRNN

Benign

0.12

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.55

PhyloP100

0.54

PrimateAI

Pathogenic

0.92

PROVEAN

Benign

0.11

REVEL

Benign

0.082

Sift

Pathogenic

0.0

Sift4G

Benign

0.23

Polyphen

0.90

Vest4

0.17

MutPred

0.25

Loss of relative solvent accessibility (P = 0.0071)

MVP

0.51

MPC

0.0011

ClinPred

0.48

GERP RS

2.3

PromoterAI

-0.028

Neutral

(source)

Varity_R

0.10

gMVP

0.22

Mutation Taster

=89/11

polymorphism

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over