ENST00000636437.1:c.457+69218C>T

Variant names:

• chr6-106132754-G-A
• rs6937876
• ENST00000636437.1:c.457+69218C>T

Variant summary

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

The ENST00000636437.1(ATG5):​c.457+69218C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.698 in 152,152 control chromosomes in the GnomAD database, including 38,482 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 0.70 (38482 hom., cov: 32)
• Consequence: ATG5 ENST00000636437.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.856
• Publications: 17 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

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 = 0.893 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATG5	ENST00000636437.1	c.457+69218C>T		intron_variant	Intron 6 of 6	5		ENSP00000490376.1
ATG5	ENST00000636335.1	n.458-54439C>T		intron_variant	Intron 6 of 8	5		ENSP00000490221.1

Frequencies

GnomAD3 genomes AF: 0.698 AC: 106116 AN: 152034 Hom.: 38410 Cov.: 32

Gnomad AFR AF: 0.900

Gnomad AMI AF: 0.618

Gnomad AMR AF: 0.698

Gnomad ASJ AF: 0.597

Gnomad EAS AF: 0.649

Gnomad SAS AF: 0.625

Gnomad FIN AF: 0.539

Gnomad MID AF: 0.655

Gnomad NFE AF: 0.616

Gnomad OTH AF: 0.676

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

GnomAD4 genome AF: 0.698 AC: 106261 AN: 152152 Hom.: 38482 Cov.: 32 AF XY: 0.694 AC XY: 51587 AN XY: 74374

African (AFR) AF: 0.900 AC: 37391 AN: 41534

American (AMR) AF: 0.698 AC: 10676 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.597 AC: 2073 AN: 3472

East Asian (EAS) AF: 0.650 AC: 3357 AN: 5166

South Asian (SAS) AF: 0.628 AC: 3030 AN: 4822

European-Finnish (FIN) AF: 0.539 AC: 5695 AN: 10574

Middle Eastern (MID) AF: 0.660 AC: 194 AN: 294

European-Non Finnish (NFE) AF: 0.616 AC: 41857 AN: 67972

Other (OTH) AF: 0.675 AC: 1427 AN: 2114

Alfa AF: 0.680 Hom.: 5864

Bravo AF: 0.721

Asia WGS AF: 0.662 AC: 2304 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.35
DANN	Benign	0.56
PhyloP100		-0.86

Splicing

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

Other links and lift over

dbSNP: rs6937876; hg19: chr6-106580629; COSMIC: COSV60263571;