ENST00000636437.1:c.457+21937G>A

Variant names:

• chr6-106180035-C-T
• rs9398071
• ENST00000636437.1:c.457+21937G>A

Variant summary

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

The ENST00000636437.1(ATG5):​c.457+21937G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.782 in 152,128 control chromosomes in the GnomAD database, including 46,876 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 0.78 (46876 hom., cov: 31)
• Consequence: ATG5 ENST00000636437.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.461
• Publications: 7 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: Labcorp Genetics (formerly Invitae), Ambry Genetics, ClinGen

ENSG00000303838 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.873 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATG5	ENST00000636437.1	TSL:5	c.457+21937G>A		intron	N/A	ENSP00000490376.1
	ATG5	ENST00000636335.1	TSL:5	n.457+21937G>A		intron	N/A	ENSP00000490221.1
	ENSG00000303838	ENST00000797436.1		n.185-1203C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.782 AC: 118923 AN: 152010 Hom.: 46855 Cov.: 31

Gnomad AFR AF: 0.835

Gnomad AMI AF: 0.805

Gnomad AMR AF: 0.684

Gnomad ASJ AF: 0.780

Gnomad EAS AF: 0.895

Gnomad SAS AF: 0.783

Gnomad FIN AF: 0.831

Gnomad MID AF: 0.791

Gnomad NFE AF: 0.756

Gnomad OTH AF: 0.778

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

GnomAD4 genome AF: 0.782 AC: 118987 AN: 152128 Hom.: 46876 Cov.: 31 AF XY: 0.785 AC XY: 58346 AN XY: 74368

African (AFR) AF: 0.835 AC: 34664 AN: 41500

American (AMR) AF: 0.683 AC: 10442 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.780 AC: 2709 AN: 3472

East Asian (EAS) AF: 0.895 AC: 4630 AN: 5176

South Asian (SAS) AF: 0.781 AC: 3767 AN: 4824

European-Finnish (FIN) AF: 0.831 AC: 8805 AN: 10596

Middle Eastern (MID) AF: 0.782 AC: 230 AN: 294

European-Non Finnish (NFE) AF: 0.756 AC: 51387 AN: 67968

Other (OTH) AF: 0.770 AC: 1622 AN: 2106

Alfa AF: 0.758 Hom.: 84658

Bravo AF: 0.774

Asia WGS AF: 0.793 AC: 2762 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.6
DANN	Benign	0.61
PhyloP100		0.46

Splicing

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

Other links and lift over

dbSNP: rs9398071; hg19: chr6-106627910;