rs2373929

Positions:

• chr7-151017725-G-A

Variant summary

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

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0890

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=-0.81).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.486 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATG9B	NM_001317056.2	c.2052+146C>T		intron_variant		ENST00000639579.2	NP_001303985.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATG9B	ENST00000639579.2	c.2052+146C>T		intron_variant		1	NM_001317056.2	ENSP00000491504	P1
ATG9B	ENST00000605952.5	c.2052+146C>T		intron_variant, NMD_transcript_variant		1		ENSP00000475737
ATG9B	ENST00000617967.4	n.946+146C>T		intron_variant, non_coding_transcript_variant		1
ATG9B	ENST00000469530.4	c.2052+146C>T		intron_variant		5		ENSP00000479879	P1

Frequencies

GnomAD3 genomes AF: 0.381 AC: 57906 AN: 151984 Hom.: 12176 Cov.: 33

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

Gnomad4 AFR exome AF: 0.203

Gnomad4 AMR exome AF: 0.558

Gnomad4 ASJ exome AF: 0.334

Gnomad4 EAS exome AF: 0.424

Gnomad4 SAS exome AF: 0.246

Gnomad4 FIN exome AF: 0.521

Gnomad4 NFE exome AF: 0.439

Gnomad4 OTH exome AF: 0.400

GnomAD4 genome AF: 0.381 AC: 57947 AN: 152102 Hom.: 12195 Cov.: 33 AF XY: 0.384 AC XY: 28554 AN XY: 74358

Gnomad4 AFR AF: 0.215

Gnomad4 AMR AF: 0.495

Gnomad4 ASJ AF: 0.346

Gnomad4 EAS AF: 0.417

Gnomad4 SAS AF: 0.238

Gnomad4 FIN AF: 0.536

Gnomad4 NFE AF: 0.442

Gnomad4 OTH AF: 0.367

Alfa AF: 0.417 Hom.: 18901

Bravo AF: 0.377

Asia WGS AF: 0.307 AC: 1067 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	4.4
DANN	Benign	0.63

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

LitVar

Other links and lift over

dbSNP: rs2373929; hg19: chr7-150714812; COSMIC: COSV52497004; COSMIC: COSV52497004;