Genetic Variant AVEN:c.516+10G>C (chr15-33875915-C-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_020371.3(AVEN):c.516+10G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.025 in 1,611,950 control chromosomes in the GnomAD database, including 3,924 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 0.053 ( 665 hom., cov: 32)

Exomes 𝑓: 0.022 ( 3259 hom. )

Consequence

AVEN
NM_020371.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.24

Publications

3 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:

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=-0.83).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.359 is higher than 0.05.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AVEN	NM_020371.3	MANE Select	c.516+10G>C		intron	N/A	NP_065104.1	Q9NQS1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
AVEN	ENST00000306730.8	TSL:1 MANE Select	c.516+10G>C	intron	N/A	ENSP00000306822.3	Q9NQS1
AVEN	ENST00000964283.1		c.609+10G>C	intron	N/A	ENSP00000634342.1
AVEN	ENST00000964282.1		c.516+10G>C	intron	N/A	ENSP00000634341.1

Frequencies

GnomAD3 genomes

AF:

0.0534

AC:

8114

AN:

152064

Hom.:

668

Cov.:

show subpopulations

Gnomad AFR

AF:

0.117

Gnomad AMI

AF:

0.00330

Gnomad AMR

AF:

0.0240

Gnomad ASJ

AF:

0.0320

Gnomad EAS

AF:

0.373

Gnomad SAS

AF:

0.0363

Gnomad FIN

AF:

0.00970

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.00720

Gnomad OTH

AF:

0.0502

GnomAD2 exomes

AF:

0.0470

AC:

11793

AN:

251162

AF XY:

0.0431

show subpopulations

Gnomad AFR exome

AF:

0.119

Gnomad AMR exome

AF:

0.0191

Gnomad ASJ exome

AF:

0.0401

Gnomad EAS exome

AF:

0.381

Gnomad FIN exome

AF:

0.00988

Gnomad NFE exome

AF:

0.00698

Gnomad OTH exome

AF:

0.0302

GnomAD4 exome

AF:

0.0220

AC:

32136

AN:

1459768

Hom.:

3259

Cov.:

AF XY:

0.0217

AC XY:

15740

AN XY:

726364

show subpopulations

African (AFR)

AF:

0.118

AC:

3929

AN:

33396

American (AMR)

AF:

0.0197

AC:

882

AN:

44708

Ashkenazi Jewish (ASJ)

AF:

0.0391

AC:

1020

AN:

26120

East Asian (EAS)

AF:

0.367

AC:

14547

AN:

39642

South Asian (SAS)

AF:

0.0230

AC:

1980

AN:

86174

European-Finnish (FIN)

AF:

0.00912

AC:

486

AN:

53298

Middle Eastern (MID)

AF:

0.0234

AC:

135

AN:

5758

European-Non Finnish (NFE)

AF:

0.00614

AC:

6822

AN:

1110346

Other (OTH)

AF:

0.0387

AC:

2335

AN:

60326

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

1224

2448

3672

4896

6120

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

534

1068

1602

2136

2670

<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:

0.0534

AC:

8121

AN:

152182

Hom.:

665

Cov.:

AF XY:

0.0540

AC XY:

4017

AN XY:

74412

show subpopulations

African (AFR)

AF:

0.117

AC:

4835

AN:

41490

American (AMR)

AF:

0.0239

AC:

365

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.0320

AC:

111

AN:

3470

East Asian (EAS)

AF:

0.373

AC:

1924

AN:

5164

South Asian (SAS)

AF:

0.0363

AC:

175

AN:

4818

European-Finnish (FIN)

AF:

0.00970

AC:

103

AN:

10614

Middle Eastern (MID)

AF:

0.0205

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00720

AC:

490

AN:

68028

Other (OTH)

AF:

0.0516

AC:

109

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

337

674

1012

1349

1686

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

196

294

392

490

<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:

0.0300

Hom.:

Bravo

AF:

0.0609

Asia WGS

AF:

0.165

AC:

573

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.34

(source)

DANN

Benign

0.56

PhyloP100

-1.2

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

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