Genetic Variant ATG9B:c.2520+63G>C (chr7-151016368-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_001317056.2(ATG9B):c.2520+63G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00333 in 1,525,344 control chromosomes in the GnomAD database, including 153 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 0.018 ( 102 hom., cov: 32)

Exomes 𝑓: 0.0017 ( 51 hom. )

Consequence

ATG9B
NM_001317056.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.604

Publications

1 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=-0.83).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0616 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATG9B	NM_001317056.2 link	c.2520+63G>C		intron_variant	Intron 11 of 13	ENST00000639579.2	NP_001303985.1	Q674R7-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
ATG9B	ENST00000639579.2 link	c.2520+63G>C	intron_variant	Intron 11 of 13	1	NM_001317056.2	ENSP00000491504.1	Q674R7-1
ATG9B	ENST00000605952.5 link	n.2520+63G>C	intron_variant	Intron 11 of 16	1		ENSP00000475737.2	Q674R7-1
ATG9B	ENST00000617967.4 link	n.1414+63G>C	intron_variant	Intron 11 of 17	1
ATG9B	ENST00000469530.4 link	c.2520+63G>C	intron_variant	Intron 11 of 12	5		ENSP00000479879.1	Q674R7-1

Frequencies

GnomAD3 genomes

AF:

0.0183

AC:

2784

AN:

152200

Hom.:

102

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0635

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00661

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000294

Gnomad OTH

AF:

0.0124

GnomAD4 exome

AF:

0.00166

AC:

2277

AN:

1373026

Hom.:

Cov.:

AF XY:

0.00142

AC XY:

959

AN XY:

674088

show subpopulations

African (AFR)

AF:

0.0568

AC:

1767

AN:

31106

American (AMR)

AF:

0.00370

AC:

129

AN:

34910

Ashkenazi Jewish (ASJ)

AF:

0.000333

AC:

AN:

24034

East Asian (EAS)

AF:

0.00

AC:

AN:

35318

South Asian (SAS)

AF:

0.000143

AC:

AN:

76810

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47876

Middle Eastern (MID)

AF:

0.00231

AC:

AN:

5624

European-Non Finnish (NFE)

AF:

0.000102

AC:

108

AN:

1060436

Other (OTH)

AF:

0.00423

AC:

241

AN:

56912

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

117

234

351

468

585

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

116

174

232

290

<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:

0.0184

AC:

2796

AN:

152318

Hom.:

102

Cov.:

AF XY:

0.0180

AC XY:

1339

AN XY:

74484

show subpopulations

African (AFR)

AF:

0.0636

AC:

2643

AN:

41556

American (AMR)

AF:

0.00660

AC:

101

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00115

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.000207

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000294

AC:

AN:

68022

Other (OTH)

AF:

0.0123

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

138

277

415

554

692

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

112

140

<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:

0.0144

Hom.:

Bravo

AF:

0.0206

Asia WGS

AF:

0.00491

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

5.2

(source)

DANN

Benign

0.29

PhyloP100

0.60

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