NM_001317056.2:c.2424-21C>G

Variant names:

• chr7-151016548-G-C
• rs3800787
• NM_001317056.2:c.2424-21C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001317056.2(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 NM_001317056.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.36
• Publications: 8 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001317056.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATG9B	NM_001317056.2	MANE Select	c.2424-21C>G		intron	N/A	NP_001303985.1	Q674R7-1
	ATG9B	NR_073169.1		n.1352-21C>G		intron	N/A
	ATG9B	NR_133652.1		n.2500-21C>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATG9B	ENST00000639579.2	TSL:1 MANE Select	c.2424-21C>G		intron	N/A	ENSP00000491504.1	Q674R7-1
	ATG9B	ENST00000605952.5	TSL:1	n.2424-21C>G		intron	N/A	ENSP00000475737.2	Q674R7-1
	ATG9B	ENST00000617967.4	TSL:1	n.1318-21C>G		intron	N/A

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

GnomAD2 exomes AF: 0.413 AC: 62391 AN: 150928 AF XY: 0.410

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 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

African (AFR) AF: 0.106 AC: 3337 AN: 31556

American (AMR) AF: 0.572 AC: 20364 AN: 35596

Ashkenazi Jewish (ASJ) AF: 0.354 AC: 8861 AN: 25048

East Asian (EAS) AF: 0.424 AC: 15128 AN: 35700

South Asian (SAS) AF: 0.438 AC: 34657 AN: 79048

European-Finnish (FIN) AF: 0.452 AC: 21521 AN: 47606

Middle Eastern (MID) AF: 0.364 AC: 2064 AN: 5676

European-Non Finnish (NFE) AF: 0.376 AC: 404814 AN: 1077444

Other (OTH) AF: 0.368 AC: 21320 AN: 57878

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

African (AFR) AF: 0.118 AC: 4872 AN: 41460

American (AMR) AF: 0.465 AC: 7086 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.372 AC: 1291 AN: 3468

East Asian (EAS) AF: 0.386 AC: 1977 AN: 5116

South Asian (SAS) AF: 0.439 AC: 2115 AN: 4818

European-Finnish (FIN) AF: 0.462 AC: 4873 AN: 10550

Middle Eastern (MID) AF: 0.397 AC: 116 AN: 292

European-Non Finnish (NFE) AF: 0.380 AC: 25805 AN: 67880

Other (OTH) AF: 0.343 AC: 720 AN: 2100

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	8.7
DANN	Benign	0.51
PhyloP100		2.4
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3800787; hg19: chr7-150713636; COSMIC: COSV52490247; COSMIC: COSV52490247;