Genetic Variant ATG9B:c.964-692A>G (chr7-151020066-T-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.964-692A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.795 in 152,068 control chromosomes in the GnomAD database, including 48,320 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 0.80 ( 48320 hom., cov: 31)

Exomes 𝑓: 0.79 ( 60 hom. )

Failed GnomAD Quality Control

Consequence

ATG9B
NM_001317056.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.11

Publications

4 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=-0.9).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.855 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATG9B	NM_001317056.2 link	c.964-692A>G		intron_variant	Intron 5 of 13	ENST00000639579.2	NP_001303985.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATG9B	ENST00000639579.2 link	c.964-692A>G		intron_variant	Intron 5 of 13	1	NM_001317056.2	ENSP00000491504.1
ATG9B	ENST00000605952.5 link	n.964-692A>G		intron_variant	Intron 5 of 16	1		ENSP00000475737.2

Frequencies

GnomAD3 genomes

AF:

0.795

AC:

120857

AN:

151950

Hom.:

48265

Cov.:

show subpopulations

Gnomad AFR

AF:

0.863

Gnomad AMI

AF:

0.782

Gnomad AMR

AF:

0.792

Gnomad ASJ

AF:

0.688

Gnomad EAS

AF:

0.780

Gnomad SAS

AF:

0.722

Gnomad FIN

AF:

0.779

Gnomad MID

AF:

0.813

Gnomad NFE

AF:

0.771

Gnomad OTH

AF:

0.768

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.789

AC:

153

AN:

194

Hom.:

Cov.:

AF XY:

0.780

AC XY:

AN XY:

118

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.788

AC:

123

AN:

156

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.765

AC:

AN:

Other (OTH)

AF:

1.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.519

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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:

0.795

AC:

120969

AN:

152068

Hom.:

48320

Cov.:

AF XY:

0.795

AC XY:

59066

AN XY:

74326

show subpopulations

African (AFR)

AF:

0.863

AC:

35780

AN:

41470

American (AMR)

AF:

0.793

AC:

12118

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.688

AC:

2387

AN:

3472

East Asian (EAS)

AF:

0.779

AC:

4021

AN:

5160

South Asian (SAS)

AF:

0.722

AC:

3472

AN:

4810

European-Finnish (FIN)

AF:

0.779

AC:

8231

AN:

10572

Middle Eastern (MID)

AF:

0.823

AC:

242

AN:

294

European-Non Finnish (NFE)

AF:

0.771

AC:

52383

AN:

67976

Other (OTH)

AF:

0.768

AC:

1623

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1265

2530

3794

5059

6324

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

868

1736

2604

3472

4340

<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:

0.775

Hom.:

72609

Bravo

AF:

0.803

Asia WGS

AF:

0.777

AC:

2701

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.88

(source)

DANN

Benign

0.46

PhyloP100

-1.1

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over