rs3918220

Positions:

• chr7-151016368-C-G

Variant summary

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

The NM_001317056.2(ATG9B):​c.2520+63G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00333 in 1,525,344 control chromosomes in the GnomAD database, including 153 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 0.018 (102 hom., cov: 32)
  • Exomes 𝑓: 0.0017 (51 hom.)
• Consequence: ATG9B NM_001317056.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.604

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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0616 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATG9B	NM_001317056.2	c.2520+63G>C		intron_variant		ENST00000639579.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATG9B	ENST00000639579.2	c.2520+63G>C		intron_variant		1	NM_001317056.2	P1
ATG9B	ENST00000605952.5	c.2520+63G>C		intron_variant, NMD_transcript_variant		1
ATG9B	ENST00000617967.4	n.1414+63G>C		intron_variant, non_coding_transcript_variant		1
ATG9B	ENST00000469530.4	c.2520+63G>C		intron_variant		5		P1

Frequencies

GnomAD3 genomes AF: 0.0183 AC: 2784 AN: 152200 Hom.: 102 Cov.: 32

Gnomad AFR AF: 0.0635

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00661

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000294

Gnomad OTH AF: 0.0124

GnomAD4 exome AF: 0.00166 AC: 2277 AN: 1373026 Hom.: 51 Cov.: 31 AF XY: 0.00142 AC XY: 959 AN XY: 674088

Gnomad4 AFR exome AF: 0.0568

Gnomad4 AMR exome AF: 0.00370

Gnomad4 ASJ exome AF: 0.000333

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000143

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000102

Gnomad4 OTH exome AF: 0.00423

GnomAD4 genome AF: 0.0184 AC: 2796 AN: 152318 Hom.: 102 Cov.: 32 AF XY: 0.0180 AC XY: 1339 AN XY: 74484

Gnomad4 AFR AF: 0.0636

Gnomad4 AMR AF: 0.00660

Gnomad4 ASJ AF: 0.00115

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000294

Gnomad4 OTH AF: 0.0123

Alfa AF: 0.0144 Hom.: 10

Bravo AF: 0.0206

Asia WGS AF: 0.00491 AC: 17 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.2
DANN	Benign	0.29

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: rs3918220; hg19: chr7-150713456;