Genetic Variant ATG9B:c.2424-21C>G (chr7-151016548-G-C) – 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.2424-21C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.376 in 1,547,394 control chromosomes in the GnomAD database, including 113,472 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 0.32 ( 9473 hom., cov: 31)

Exomes 𝑓: 0.38 ( 103999 hom. )

Consequence

ATG9B
NM_001317056.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.36

Publications

8 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=-0.84).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.456 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.2424-21C>G	intron	N/A	NP_001303985.1	Q674R7-1
ATG9B	NR_073169.1		n.1352-21C>G	intron	N/A
ATG9B	NR_133652.1		n.2500-21C>G	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ATG9B	ENST00000639579.2	TSL:1 MANE Select	c.2424-21C>G	intron	N/A	ENSP00000491504.1	Q674R7-1
ATG9B	ENST00000605952.5	TSL:1	n.2424-21C>G	intron	N/A	ENSP00000475737.2	Q674R7-1
ATG9B	ENST00000617967.4	TSL:1	n.1318-21C>G	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.324

AC:

49216

AN:

151724

Hom.:

9465

Cov.:

show subpopulations

Gnomad AFR

AF:

0.118

Gnomad AMI

AF:

0.419

Gnomad AMR

AF:

0.464

Gnomad ASJ

AF:

0.372

Gnomad EAS

AF:

0.387

Gnomad SAS

AF:

0.440

Gnomad FIN

AF:

0.462

Gnomad MID

AF:

0.392

Gnomad NFE

AF:

0.380

Gnomad OTH

AF:

0.346

GnomAD2 exomes

AF:

0.413

AC:

62391

AN:

150928

AF XY:

0.410

show subpopulations

Gnomad AFR exome

AF:

0.107

Gnomad AMR exome

AF:

0.580

Gnomad ASJ exome

AF:

0.357

Gnomad EAS exome

AF:

0.378

Gnomad FIN exome

AF:

0.459

Gnomad NFE exome

AF:

0.377

Gnomad OTH exome

AF:

0.404

GnomAD4 exome

AF:

0.381

AC:

532066

AN:

1395552

Hom.:

103999

Cov.:

AF XY:

0.383

AC XY:

263390

AN XY:

688062

show subpopulations

African (AFR)

AF:

0.106

AC:

3337

AN:

31556

American (AMR)

AF:

0.572

AC:

20364

AN:

35596

Ashkenazi Jewish (ASJ)

AF:

0.354

AC:

8861

AN:

25048

East Asian (EAS)

AF:

0.424

AC:

15128

AN:

35700

South Asian (SAS)

AF:

0.438

AC:

34657

AN:

79048

European-Finnish (FIN)

AF:

0.452

AC:

21521

AN:

47606

Middle Eastern (MID)

AF:

0.364

AC:

2064

AN:

5676

European-Non Finnish (NFE)

AF:

0.376

AC:

404814

AN:

1077444

Other (OTH)

AF:

0.368

AC:

21320

AN:

57878

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

18888

37776

56664

75552

94440

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12970

25940

38910

51880

64850

<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:

0.324

AC:

49235

AN:

151842

Hom.:

9473

Cov.:

AF XY:

0.333

AC XY:

24697

AN XY:

74206

show subpopulations

African (AFR)

AF:

0.118

AC:

4872

AN:

41460

American (AMR)

AF:

0.465

AC:

7086

AN:

15250

Ashkenazi Jewish (ASJ)

AF:

0.372

AC:

1291

AN:

3468

East Asian (EAS)

AF:

0.386

AC:

1977

AN:

5116

South Asian (SAS)

AF:

0.439

AC:

2115

AN:

4818

European-Finnish (FIN)

AF:

0.462

AC:

4873

AN:

10550

Middle Eastern (MID)

AF:

0.397

AC:

116

AN:

292

European-Non Finnish (NFE)

AF:

0.380

AC:

25805

AN:

67880

Other (OTH)

AF:

0.343

AC:

720

AN:

2100

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

1543

3085

4628

6170

7713

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

488

976

1464

1952

2440

<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:

0.290

Hom.:

1389

Bravo

AF:

0.318

Asia WGS

AF:

0.413

AC:

1432

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

8.7

(source)

DANN

Benign

0.51

PhyloP100

2.4

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