7-151016548-G-C

Position:

• chr7-151016548-G-C

Variant summary

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

The ENST00000639579.2(ATG9B):​c.2424-21C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.376 in 1,547,394 control chromosomes in the GnomAD database, including 113,472 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 0.32 (9473 hom., cov: 31)
  • Exomes 𝑓: 0.38 (103999 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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.456 is higher than 0.05.

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes AF: 0.324 AC: 49216 AN: 151724 Hom.: 9465 Cov.: 31

Gnomad AFR AF: 0.118

Gnomad AMI AF: 0.419

Gnomad AMR AF: 0.464

Gnomad ASJ AF: 0.372

Gnomad EAS AF: 0.387

Gnomad SAS AF: 0.440

Gnomad FIN AF: 0.462

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.380

Gnomad OTH AF: 0.346

GnomAD3 exomes AF: 0.413 AC: 62391 AN: 150928 Hom.: 13838 AF XY: 0.410 AC XY: 32912 AN XY: 80288

Gnomad AFR exome AF: 0.107

Gnomad AMR exome AF: 0.580

Gnomad ASJ exome AF: 0.357

Gnomad EAS exome AF: 0.378

Gnomad SAS exome AF: 0.441

Gnomad FIN exome AF: 0.459

Gnomad NFE exome AF: 0.377

Gnomad OTH exome AF: 0.404

GnomAD4 exome AF: 0.381 AC: 532066 AN: 1395552 Hom.: 103999 Cov.: 36 AF XY: 0.383 AC XY: 263390 AN XY: 688062

Gnomad4 AFR exome AF: 0.106

Gnomad4 AMR exome AF: 0.572

Gnomad4 ASJ exome AF: 0.354

Gnomad4 EAS exome AF: 0.424

Gnomad4 SAS exome AF: 0.438

Gnomad4 FIN exome AF: 0.452

Gnomad4 NFE exome AF: 0.376

Gnomad4 OTH exome AF: 0.368

GnomAD4 genome AF: 0.324 AC: 49235 AN: 151842 Hom.: 9473 Cov.: 31 AF XY: 0.333 AC XY: 24697 AN XY: 74206

Gnomad4 AFR AF: 0.118

Gnomad4 AMR AF: 0.465

Gnomad4 ASJ AF: 0.372

Gnomad4 EAS AF: 0.386

Gnomad4 SAS AF: 0.439

Gnomad4 FIN AF: 0.462

Gnomad4 NFE AF: 0.380

Gnomad4 OTH AF: 0.343

Alfa AF: 0.290 Hom.: 1389

Bravo AF: 0.318

Asia WGS AF: 0.413 AC: 1432 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	8.7
DANN	Benign	0.51

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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; COSMIC: COSV52490247; COSMIC: COSV52490247;