Genetic Variant NM_001317056.2:c.2052+146C>T (chr7-151017725-G-A) – 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.2052+146C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.417 in 995,538 control chromosomes in the GnomAD database, including 90,586 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 0.38 ( 12195 hom., cov: 33)

Exomes 𝑓: 0.42 ( 78391 hom. )

Consequence

ATG9B
NM_001317056.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0890

Publications

29 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=-0.81).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.486 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
ATG9B	NM_001317056.2	MANE Select	c.2052+146C>T	intron	N/A	NP_001303985.1
ATG9B	NR_073169.1		n.980+146C>T	intron	N/A
ATG9B	NR_133652.1		n.2128+146C>T	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
ATG9B	ENST00000639579.2	TSL:1 MANE Select	c.2052+146C>T	intron	N/A	ENSP00000491504.1
ATG9B	ENST00000605952.5	TSL:1	n.2052+146C>T	intron	N/A	ENSP00000475737.2
ATG9B	ENST00000617967.4	TSL:1	n.946+146C>T	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.381

AC:

57906

AN:

151984

Hom.:

12176

Cov.:

show subpopulations

Gnomad AFR

AF:

0.215

Gnomad AMI

AF:

0.380

Gnomad AMR

AF:

0.494

Gnomad ASJ

AF:

0.346

Gnomad EAS

AF:

0.416

Gnomad SAS

AF:

0.237

Gnomad FIN

AF:

0.536

Gnomad MID

AF:

0.363

Gnomad NFE

AF:

0.442

Gnomad OTH

AF:

0.372

GnomAD4 exome

AF:

0.423

AC:

356802

AN:

843436

Hom.:

78391

AF XY:

0.416

AC XY:

175427

AN XY:

421878

show subpopulations

African (AFR)

AF:

0.203

AC:

3993

AN:

19662

American (AMR)

AF:

0.558

AC:

10279

AN:

18412

Ashkenazi Jewish (ASJ)

AF:

0.334

AC:

5355

AN:

16018

East Asian (EAS)

AF:

0.424

AC:

13776

AN:

32494

South Asian (SAS)

AF:

0.246

AC:

12780

AN:

51928

European-Finnish (FIN)

AF:

0.521

AC:

18932

AN:

36332

Middle Eastern (MID)

AF:

0.336

AC:

913

AN:

2720

European-Non Finnish (NFE)

AF:

0.439

AC:

275254

AN:

627070

Other (OTH)

AF:

0.400

AC:

15520

AN:

38800

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

9849

19697

29546

39394

49243

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7044

14088

21132

28176

35220

<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:

0.381

AC:

57947

AN:

152102

Hom.:

12195

Cov.:

AF XY:

0.384

AC XY:

28554

AN XY:

74358

show subpopulations

African (AFR)

AF:

0.215

AC:

8926

AN:

41496

American (AMR)

AF:

0.495

AC:

7573

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.346

AC:

1200

AN:

3468

East Asian (EAS)

AF:

0.417

AC:

2150

AN:

5162

South Asian (SAS)

AF:

0.238

AC:

1147

AN:

4816

European-Finnish (FIN)

AF:

0.536

AC:

5669

AN:

10578

Middle Eastern (MID)

AF:

0.384

AC:

112

AN:

292

European-Non Finnish (NFE)

AF:

0.442

AC:

30052

AN:

67984

Other (OTH)

AF:

0.367

AC:

772

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1800

3601

5401

7202

9002

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

548

1096

1644

2192

2740

<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:

0.414

Hom.:

43699

Bravo

AF:

0.377

Asia WGS

AF:

0.307

AC:

1067

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

4.4

(source)

DANN

Benign

0.63

PhyloP100

-0.089

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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