6-106111752-C-G

Variant names:

• chr6-106111752-C-G
• rs578653
• ENST00000636437.1:c.458-64927G>C

Variant summary

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

The ENST00000636437.1(ATG5):​c.458-64927G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.153 in 151,766 control chromosomes in the GnomAD database, including 2,005 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 0.15 (2005 hom., cov: 30)
• Consequence: ATG5 ENST00000636437.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.792
• Publications: 5 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=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.181 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.458-64927G>C		intron_variant	Intron 6 of 6	5		ENSP00000490376.1
ATG5	ENST00000636335.1	n.458-33437G>C		intron_variant	Intron 6 of 8	5		ENSP00000490221.1

Frequencies

GnomAD3 genomes AF: 0.153 AC: 23237 AN: 151648 Hom.: 2004 Cov.: 30

Gnomad AFR AF: 0.109

Gnomad AMI AF: 0.205

Gnomad AMR AF: 0.137

Gnomad ASJ AF: 0.164

Gnomad EAS AF: 0.00849

Gnomad SAS AF: 0.193

Gnomad FIN AF: 0.247

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.176

Gnomad OTH AF: 0.161

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

GnomAD4 genome AF: 0.153 AC: 23251 AN: 151766 Hom.: 2005 Cov.: 30 AF XY: 0.157 AC XY: 11617 AN XY: 74148

African (AFR) AF: 0.109 AC: 4508 AN: 41372

American (AMR) AF: 0.138 AC: 2099 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.164 AC: 567 AN: 3464

East Asian (EAS) AF: 0.00870 AC: 45 AN: 5172

South Asian (SAS) AF: 0.192 AC: 922 AN: 4808

European-Finnish (FIN) AF: 0.247 AC: 2587 AN: 10468

Middle Eastern (MID) AF: 0.187 AC: 55 AN: 294

European-Non Finnish (NFE) AF: 0.176 AC: 11946 AN: 67942

Other (OTH) AF: 0.160 AC: 336 AN: 2100

Alfa AF: 0.160 Hom.: 239

Bravo AF: 0.142

Asia WGS AF: 0.114 AC: 394 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.5
DANN	Benign	0.54
PhyloP100		-0.79

Splicing

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

Other links and lift over

dbSNP: rs578653; hg19: chr6-106559627; COSMIC: COSV64846854; COSMIC: COSV64846854;