chr6-106153480-A-C

Variant names:

• chr6-106153480-A-C
• rs9372118
• ENST00000636437.1:c.457+48492T>G

Variant summary

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

The ENST00000636437.1(ATG5):​c.457+48492T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.458 in 152,068 control chromosomes in the GnomAD database, including 16,570 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 0.46 (16570 hom., cov: 33)
• Consequence: ATG5 ENST00000636437.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.547
• Publications: 4 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.577 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+48492T>G		intron_variant	Intron 6 of 6	5		ENSP00000490376.1
ATG5	ENST00000636335.1	n.457+48492T>G		intron_variant	Intron 6 of 8	5		ENSP00000490221.1

Frequencies

GnomAD3 genomes AF: 0.457 AC: 69470 AN: 151950 Hom.: 16522 Cov.: 33

Gnomad AFR AF: 0.583

Gnomad AMI AF: 0.396

Gnomad AMR AF: 0.419

Gnomad ASJ AF: 0.439

Gnomad EAS AF: 0.531

Gnomad SAS AF: 0.514

Gnomad FIN AF: 0.392

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.392

Gnomad OTH AF: 0.439

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

GnomAD4 genome AF: 0.458 AC: 69578 AN: 152068 Hom.: 16570 Cov.: 33 AF XY: 0.460 AC XY: 34158 AN XY: 74320

African (AFR) AF: 0.583 AC: 24201 AN: 41486

American (AMR) AF: 0.419 AC: 6394 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.439 AC: 1525 AN: 3470

East Asian (EAS) AF: 0.531 AC: 2750 AN: 5176

South Asian (SAS) AF: 0.513 AC: 2479 AN: 4830

European-Finnish (FIN) AF: 0.392 AC: 4137 AN: 10558

Middle Eastern (MID) AF: 0.408 AC: 120 AN: 294

European-Non Finnish (NFE) AF: 0.392 AC: 26674 AN: 67976

Other (OTH) AF: 0.445 AC: 938 AN: 2108

Alfa AF: 0.364 Hom.: 2345

Bravo AF: 0.461

Asia WGS AF: 0.545 AC: 1894 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.5
DANN	Benign	0.81
PhyloP100		-0.55

Splicing

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

Other links and lift over

dbSNP: rs9372118; hg19: chr6-106601355; COSMIC: COSV60263665;