rs3918220

Variant names:

• chr7-151016368-C-A
• rs3918220
• NM_001317056.2:c.2520+63G>T

Your query was ambiguous. Multiple possible variants found:

• chr7-151016368-C-A
• chr7-151016368-C-G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001317056.2(ATG9B):​c.2520+63G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000728 in 1,373,046 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 7.3e-7 (0 hom.)
• Consequence: ATG9B NM_001317056.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.604
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATG9B	NM_001317056.2	c.2520+63G>T		intron_variant	Intron 11 of 13	ENST00000639579.2	NP_001303985.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATG9B	ENST00000639579.2	c.2520+63G>T		intron_variant	Intron 11 of 13	1	NM_001317056.2	ENSP00000491504.1
ATG9B	ENST00000605952.5	n.2520+63G>T		intron_variant	Intron 11 of 16	1		ENSP00000475737.2
ATG9B	ENST00000617967.4	n.1414+63G>T		intron_variant	Intron 11 of 17	1
ATG9B	ENST00000469530.4	c.2520+63G>T		intron_variant	Intron 11 of 12	5		ENSP00000479879.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.28e-7 AC: 1 AN: 1373046 Hom.: 0 Cov.: 31 AF XY: 0.00000148 AC XY: 1 AN XY: 674096

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 31124

American (AMR) AF: 0.00 AC: 0 AN: 34910

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24034

East Asian (EAS) AF: 0.00 AC: 0 AN: 35318

South Asian (SAS) AF: 0.0000130 AC: 1 AN: 76810

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47876

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5624

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1060438

Other (OTH) AF: 0.00 AC: 0 AN: 56912

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.0
DANN	Benign	0.32
PhyloP100		0.60

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

Other links and lift over

dbSNP: rs3918220; hg19: chr7-150713456;