7-151023221-G-T

Position:

• chr7-151023221-G-T

Variant summary

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

The NM_001317056.2(ATG9B):​c.660-15C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.187 in 1,613,480 control chromosomes in the GnomAD database, including 32,765 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 0.20 (3550 hom., cov: 32)
  • Exomes 𝑓: 0.19 (29215 hom.)
• Consequence: ATG9B NM_001317056.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.633

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.417 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATG9B	NM_001317056.2	c.660-15C>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.660-15C>A		intron_variant		1	NM_001317056.2	ENSP00000491504.1
ATG9B	ENST00000605952.5	n.660-15C>A		intron_variant		1		ENSP00000475737.2

Frequencies

GnomAD3 genomes AF: 0.200 AC: 30308 AN: 151736 Hom.: 3533 Cov.: 32

Gnomad AFR AF: 0.183

Gnomad AMI AF: 0.105

Gnomad AMR AF: 0.348

Gnomad ASJ AF: 0.149

Gnomad EAS AF: 0.432

Gnomad SAS AF: 0.130

Gnomad FIN AF: 0.205

Gnomad MID AF: 0.205

Gnomad NFE AF: 0.167

Gnomad OTH AF: 0.204

GnomAD3 exomes AF: 0.237 AC: 58901 AN: 249024 Hom.: 9185 AF XY: 0.220 AC XY: 29711 AN XY: 135134

Gnomad AFR exome AF: 0.185

Gnomad AMR exome AF: 0.505

Gnomad ASJ exome AF: 0.145

Gnomad EAS exome AF: 0.416

Gnomad SAS exome AF: 0.140

Gnomad FIN exome AF: 0.211

Gnomad NFE exome AF: 0.173

Gnomad OTH exome AF: 0.226

GnomAD4 exome AF: 0.186 AC: 271430 AN: 1461630 Hom.: 29215 Cov.: 36 AF XY: 0.182 AC XY: 132452 AN XY: 727112

Gnomad4 AFR exome AF: 0.184

Gnomad4 AMR exome AF: 0.490

Gnomad4 ASJ exome AF: 0.145

Gnomad4 EAS exome AF: 0.435

Gnomad4 SAS exome AF: 0.138

Gnomad4 FIN exome AF: 0.208

Gnomad4 NFE exome AF: 0.168

Gnomad4 OTH exome AF: 0.187

GnomAD4 genome AF: 0.200 AC: 30343 AN: 151850 Hom.: 3550 Cov.: 32 AF XY: 0.204 AC XY: 15155 AN XY: 74266

Gnomad4 AFR AF: 0.183

Gnomad4 AMR AF: 0.349

Gnomad4 ASJ AF: 0.149

Gnomad4 EAS AF: 0.432

Gnomad4 SAS AF: 0.130

Gnomad4 FIN AF: 0.205

Gnomad4 NFE AF: 0.167

Gnomad4 OTH AF: 0.201

Alfa AF: 0.131 Hom.: 472

Bravo AF: 0.217

Asia WGS AF: 0.262 AC: 910 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.12
DANN	Benign	0.50

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: rs12666075; hg19: chr7-150720308; COSMIC: COSV65059918; COSMIC: COSV65059918;