rs6568431

Positions:

• chr6-106140931-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000636437.1(ATG5):​c.457+61041T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.608 in 152,130 control chromosomes in the GnomAD database, including 28,291 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 0.61 (28291 hom., cov: 33)
• Consequence: ATG5 ENST00000636437.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.759

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.642 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATG5	ENST00000636437.1	c.457+61041T>G		intron_variant		5		ENSP00000490376
ATG5	ENST00000636335.1	c.457+61041T>G		intron_variant, NMD_transcript_variant		5		ENSP00000490221

Frequencies

GnomAD3 genomes AF: 0.608 AC: 92415 AN: 152012 Hom.: 28261 Cov.: 33

Gnomad AFR AF: 0.591

Gnomad AMI AF: 0.614

Gnomad AMR AF: 0.653

Gnomad ASJ AF: 0.592

Gnomad EAS AF: 0.645

Gnomad SAS AF: 0.624

Gnomad FIN AF: 0.538

Gnomad MID AF: 0.644

Gnomad NFE AF: 0.616

Gnomad OTH AF: 0.618

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

GnomAD4 genome AF: 0.608 AC: 92509 AN: 152130 Hom.: 28291 Cov.: 33 AF XY: 0.606 AC XY: 45039 AN XY: 74382

Gnomad4 AFR AF: 0.591

Gnomad4 AMR AF: 0.653

Gnomad4 ASJ AF: 0.592

Gnomad4 EAS AF: 0.646

Gnomad4 SAS AF: 0.627

Gnomad4 FIN AF: 0.538

Gnomad4 NFE AF: 0.616

Gnomad4 OTH AF: 0.618

Alfa AF: 0.620 Hom.: 39548

Bravo AF: 0.619

Asia WGS AF: 0.637 AC: 2218 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.5
DANN	Benign	0.68

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6568431; hg19: chr6-106588806; COSMIC: COSV55571756;