ENST00000636437.1:c.458-73334G>A

Variant names:

• chr6-106120159-C-T
• rs548234
• ENST00000636437.1:c.458-73334G>A

Variant summary

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

The ENST00000636437.1(ATG5):​c.458-73334G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.761 in 152,168 control chromosomes in the GnomAD database, including 44,979 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 0.76 (44979 hom., cov: 32)
• Consequence: ATG5 ENST00000636437.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.266
• Publications: 108 publications found

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]

ATG5 Gene-Disease associations (from GenCC):

• spinocerebellar ataxia, autosomal recessive 25

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.913 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000636437.1. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATG5	ENST00000636437.1	TSL:5	c.458-73334G>A		intron	N/A	ENSP00000490376.1	A0A1B0GV54
	ATG5	ENST00000636335.1	TSL:5	n.458-41844G>A		intron	N/A	ENSP00000490221.1	A0A1B0GUS1

Frequencies

GnomAD3 genomes AF: 0.761 AC: 115672 AN: 152050 Hom.: 44895 Cov.: 32

Gnomad AFR AF: 0.920

Gnomad AMI AF: 0.701

Gnomad AMR AF: 0.783

Gnomad ASJ AF: 0.677

Gnomad EAS AF: 0.712

Gnomad SAS AF: 0.801

Gnomad FIN AF: 0.679

Gnomad MID AF: 0.725

Gnomad NFE AF: 0.678

Gnomad OTH AF: 0.746

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

GnomAD4 genome AF: 0.761 AC: 115823 AN: 152168 Hom.: 44979 Cov.: 32 AF XY: 0.763 AC XY: 56752 AN XY: 74396

African (AFR) AF: 0.921 AC: 38249 AN: 41548

American (AMR) AF: 0.784 AC: 11985 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.677 AC: 2349 AN: 3470

East Asian (EAS) AF: 0.713 AC: 3689 AN: 5174

South Asian (SAS) AF: 0.802 AC: 3875 AN: 4830

European-Finnish (FIN) AF: 0.679 AC: 7173 AN: 10568

Middle Eastern (MID) AF: 0.731 AC: 215 AN: 294

European-Non Finnish (NFE) AF: 0.678 AC: 46076 AN: 67976

Other (OTH) AF: 0.746 AC: 1574 AN: 2110

Alfa AF: 0.704 Hom.: 132152

Bravo AF: 0.775

Asia WGS AF: 0.779 AC: 2709 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.9
DANN	Benign	0.42
PhyloP100		0.27

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs548234; hg19: chr6-106568034;