rs2373929

Variant names:

• chr7-151017725-G-A
• rs2373929
• NM_001317056.2:c.2052+146C>T

Your query was ambiguous. Multiple possible variants found:

• chr7-151017725-G-A
• chr7-151017725-G-C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 29 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=-0.81).
• 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 rank	MANE	Protein	UniProt
ATG9B	NM_001317056.2	c.2052+146C>T		intron_variant	Intron 8 of 13	ENST00000639579.2	NP_001303985.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATG9B	ENST00000639579.2	c.2052+146C>T		intron_variant	Intron 8 of 13	1	NM_001317056.2	ENSP00000491504.1
ATG9B	ENST00000605952.5	n.2052+146C>T		intron_variant	Intron 8 of 16	1		ENSP00000475737.2
ATG9B	ENST00000617967.4	n.946+146C>T		intron_variant	Intron 8 of 17	1
ATG9B	ENST00000469530.4	c.2052+146C>T		intron_variant	Intron 8 of 12	5		ENSP00000479879.1

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

African (AFR) AF: 0.203 AC: 3993 AN: 19662

American (AMR) AF: 0.558 AC: 10279 AN: 18412

Ashkenazi Jewish (ASJ) AF: 0.334 AC: 5355 AN: 16018

East Asian (EAS) AF: 0.424 AC: 13776 AN: 32494

South Asian (SAS) AF: 0.246 AC: 12780 AN: 51928

European-Finnish (FIN) AF: 0.521 AC: 18932 AN: 36332

Middle Eastern (MID) AF: 0.336 AC: 913 AN: 2720

European-Non Finnish (NFE) AF: 0.439 AC: 275254 AN: 627070

Other (OTH) AF: 0.400 AC: 15520 AN: 38800

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

African (AFR) AF: 0.215 AC: 8926 AN: 41496

American (AMR) AF: 0.495 AC: 7573 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.346 AC: 1200 AN: 3468

East Asian (EAS) AF: 0.417 AC: 2150 AN: 5162

South Asian (SAS) AF: 0.238 AC: 1147 AN: 4816

European-Finnish (FIN) AF: 0.536 AC: 5669 AN: 10578

Middle Eastern (MID) AF: 0.384 AC: 112 AN: 292

European-Non Finnish (NFE) AF: 0.442 AC: 30052 AN: 67984

Other (OTH) AF: 0.367 AC: 772 AN: 2104

Alfa AF: 0.414 Hom.: 43699

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
PhyloP100		-0.089
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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