Genetic Variant ATG9B:c.660-15C>A (chr7-151023221-G-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_001317056.2(ATG9B):c.660-15C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.187 in 1,613,480 control chromosomes in the GnomAD database, including 32,765 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as (no stars).

Frequency

Genomes: 𝑓 0.20 ( 3550 hom., cov: 32)

Exomes 𝑓: 0.19 ( 29215 hom. )

Consequence

ATG9B
NM_001317056.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.633

Publications

9 publications found

Variant links:

Genes affected

ATG9B (HGNC:21899): (autophagy related 9B) This gene functions in the regulation of autophagy, a lysosomal degradation pathway. This gene also functions as an antisense transcript in the posttranscriptional regulation of the endothelial nitric oxide synthase 3 gene, which has 3' overlap with this gene on the opposite strand. Mutations in this gene and disruption of the autophagy process have been associated with multiple cancers. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2012]

ATG9B 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=-0.88).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.417 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001317056.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ATG9B	NM_001317056.2	MANE Select	c.660-15C>A	intron	N/A	NP_001303985.1	Q674R7-1
ATG9B	NR_073169.1		n.343-15C>A	intron	N/A
ATG9B	NR_133652.1		n.736-15C>A	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ATG9B	ENST00000639579.2	TSL:1 MANE Select	c.660-15C>A	intron	N/A	ENSP00000491504.1	Q674R7-1
ATG9B	ENST00000605952.5	TSL:1	n.660-15C>A	intron	N/A	ENSP00000475737.2	Q674R7-1
ATG9B	ENST00000617967.4	TSL:1	n.309-15C>A	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.200

AC:

30308

AN:

151736

Hom.:

3533

Cov.:

show subpopulations

Gnomad AFR

AF:

0.183

Gnomad AMI

AF:

0.105

Gnomad AMR

AF:

0.348

Gnomad ASJ

AF:

0.149

Gnomad EAS

AF:

0.432

Gnomad SAS

AF:

0.130

Gnomad FIN

AF:

0.205

Gnomad MID

AF:

0.205

Gnomad NFE

AF:

0.167

Gnomad OTH

AF:

0.204

GnomAD2 exomes

AF:

0.237

AC:

58901

AN:

249024

AF XY:

0.220

show subpopulations

Gnomad AFR exome

AF:

0.185

Gnomad AMR exome

AF:

0.505

Gnomad ASJ exome

AF:

0.145

Gnomad EAS exome

AF:

0.416

Gnomad FIN exome

AF:

0.211

Gnomad NFE exome

AF:

0.173

Gnomad OTH exome

AF:

0.226

GnomAD4 exome

AF:

0.186

AC:

271430

AN:

1461630

Hom.:

29215

Cov.:

AF XY:

0.182

AC XY:

132452

AN XY:

727112

show subpopulations

African (AFR)

AF:

0.184

AC:

6171

AN:

33474

American (AMR)

AF:

0.490

AC:

21934

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.145

AC:

3795

AN:

26130

East Asian (EAS)

AF:

0.435

AC:

17285

AN:

39698

South Asian (SAS)

AF:

0.138

AC:

11858

AN:

86222

European-Finnish (FIN)

AF:

0.208

AC:

11111

AN:

53356

Middle Eastern (MID)

AF:

0.167

AC:

961

AN:

5768

European-Non Finnish (NFE)

AF:

0.168

AC:

187014

AN:

1111876

Other (OTH)

AF:

0.187

AC:

11301

AN:

60384

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

12810

25620

38431

51241

64051

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6880

13760

20640

27520

34400

<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:

0.200

AC:

30343

AN:

151850

Hom.:

3550

Cov.:

AF XY:

0.204

AC XY:

15155

AN XY:

74266

show subpopulations

African (AFR)

AF:

0.183

AC:

7524

AN:

41188

American (AMR)

AF:

0.349

AC:

5335

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.149

AC:

517

AN:

3470

East Asian (EAS)

AF:

0.432

AC:

2231

AN:

5166

South Asian (SAS)

AF:

0.130

AC:

629

AN:

4824

European-Finnish (FIN)

AF:

0.205

AC:

2174

AN:

10602

Middle Eastern (MID)

AF:

0.207

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.167

AC:

11352

AN:

68004

Other (OTH)

AF:

0.201

AC:

425

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1209

2418

3628

4837

6046

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

312

624

936

1248

1560

<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:

0.170

Hom.:

1456

Bravo

AF:

0.217

Asia WGS

AF:

0.262

AC:

910

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.12

(source)

DANN

Benign

0.50

PhyloP100

-0.63

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over