7-151016548-G-T

Position:

• chr7-151016548-G-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000639579.2(ATG9B):​c.2424-21C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000246 in 1,547,650 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000026 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000024 (0 hom.)
• Consequence: ATG9B ENST00000639579.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.36

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATG9B	NM_001317056.2	c.2424-21C>A		intron_variant		ENST00000639579.2	NP_001303985.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATG9B	ENST00000639579.2	c.2424-21C>A		intron_variant		1	NM_001317056.2	ENSP00000491504	P1
ATG9B	ENST00000605952.5	c.2424-21C>A		intron_variant, NMD_transcript_variant		1		ENSP00000475737
ATG9B	ENST00000617967.4	n.1318-21C>A		intron_variant, non_coding_transcript_variant		1
ATG9B	ENST00000469530.4	c.2424-21C>A		intron_variant		5		ENSP00000479879	P1

Frequencies

GnomAD3 genomes AF: 0.0000264 AC: 4 AN: 151790 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000442

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0000133 AC: 2 AN: 150928 Hom.: 0 AF XY: 0.0000125 AC XY: 1 AN XY: 80288

Gnomad AFR exome AF: 0.000129

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000171

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000244 AC: 34 AN: 1395860 Hom.: 0 Cov.: 36 AF XY: 0.0000218 AC XY: 15 AN XY: 688222

Gnomad4 AFR exome AF: 0.0000317

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000126

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000297

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0000264 AC: 4 AN: 151790 Hom.: 0 Cov.: 31 AF XY: 0.0000270 AC XY: 2 AN XY: 74110

Gnomad4 AFR AF: 0.0000242

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000442

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	8.9
DANN	Benign	0.65

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs3800787; hg19: chr7-150713636;