rs9486306

Variant names:

• chr6-106213655-T-G
• rs9486306
• NM_004849.4:c.574-11566A>C

Variant summary

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

The NM_004849.4(ATG5):​c.574-11566A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.178 in 152,096 control chromosomes in the GnomAD database, including 2,867 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 0.18 (2867 hom., cov: 32)
• Consequence: ATG5 NM_004849.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.33

Genes affected

ATG5 (HGNC:589): (autophagy related 5) The protein encoded by this gene, in combination with autophagy protein 12, functions as an E1-like activating enzyme in a ubiquitin-like conjugating system. The encoded protein is involved in several cellular processes, including autophagic vesicle formation, mitochondrial quality control after oxidative damage, negative regulation of the innate antiviral immune response, lymphocyte development and proliferation, MHC II antigen presentation, adipocyte differentiation, and apoptosis. Several transcript variants encoding different protein isoforms have been found for this gene. [provided by RefSeq, Sep 2015]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.288 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATG5	NM_004849.4	c.574-11566A>C		intron_variant	Intron 6 of 7	ENST00000369076.8	NP_004840.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATG5	ENST00000369076.8	c.574-11566A>C		intron_variant	Intron 6 of 7	1	NM_004849.4	ENSP00000358072.3

Frequencies

GnomAD3 genomes AF: 0.178 AC: 26981 AN: 151978 Hom.: 2860 Cov.: 32

Gnomad AFR AF: 0.293

Gnomad AMI AF: 0.101

Gnomad AMR AF: 0.132

Gnomad ASJ AF: 0.120

Gnomad EAS AF: 0.0831

Gnomad SAS AF: 0.143

Gnomad FIN AF: 0.122

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.141

Gnomad OTH AF: 0.160

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.178 AC: 27016 AN: 152096 Hom.: 2867 Cov.: 32 AF XY: 0.175 AC XY: 13037 AN XY: 74358

Gnomad4 AFR AF: 0.293

Gnomad4 AMR AF: 0.132

Gnomad4 ASJ AF: 0.120

Gnomad4 EAS AF: 0.0835

Gnomad4 SAS AF: 0.143

Gnomad4 FIN AF: 0.122

Gnomad4 NFE AF: 0.141

Gnomad4 OTH AF: 0.165

Alfa AF: 0.151 Hom.: 888

Bravo AF: 0.179

Asia WGS AF: 0.150 AC: 519 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.026
DANN	Benign	0.36

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: rs9486306; hg19: chr6-106661530;