chr7-151020066-T-C

Position:

• chr7-151020066-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.11

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
ATG9B	NM_001317056.2	c.964-692A>G		intron_variant		ENST00000639579.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATG9B	ENST00000639579.2	c.964-692A>G		intron_variant		1	NM_001317056.2	P1

Frequencies

GnomAD3 genomes AF: 0.795 AC: 120857 AN: 151950 Hom.: 48265 Cov.: 31

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.: 60 Cov.: 0 AF XY: 0.780 AC XY: 92 AN XY: 118

Gnomad4 FIN exome AF: 0.788

Gnomad4 NFE exome AF: 0.765

Gnomad4 OTH exome AF: 1.00

GnomAD4 genome AF: 0.795 AC: 120969 AN: 152068 Hom.: 48320 Cov.: 31 AF XY: 0.795 AC XY: 59066 AN XY: 74326

Gnomad4 AFR AF: 0.863

Gnomad4 AMR AF: 0.793

Gnomad4 ASJ AF: 0.688

Gnomad4 EAS AF: 0.779

Gnomad4 SAS AF: 0.722

Gnomad4 FIN AF: 0.779

Gnomad4 NFE AF: 0.771

Gnomad4 OTH AF: 0.768

Alfa AF: 0.768 Hom.: 49128

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
DANN	Benign	0.46

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

LitVar

Other links and lift over

dbSNP: rs6464119; hg19: chr7-150717153;