6-106129632-A-G

Position:

• chr6-106129632-A-G

Variant summary

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

The ENST00000636437.1(ATG5):​c.457+72340T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.428 in 152,102 control chromosomes in the GnomAD database, including 15,876 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 0.43 (15876 hom., cov: 32)
• Consequence: ATG5 ENST00000636437.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.232

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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.664 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+72340T>C		intron_variant		5		ENSP00000490376
ATG5	ENST00000636335.1	c.458-51317T>C		intron_variant, NMD_transcript_variant		5		ENSP00000490221

Frequencies

GnomAD3 genomes AF: 0.428 AC: 64980 AN: 151984 Hom.: 15821 Cov.: 32

Gnomad AFR AF: 0.670

Gnomad AMI AF: 0.370

Gnomad AMR AF: 0.342

Gnomad ASJ AF: 0.312

Gnomad EAS AF: 0.463

Gnomad SAS AF: 0.307

Gnomad FIN AF: 0.288

Gnomad MID AF: 0.386

Gnomad NFE AF: 0.334

Gnomad OTH AF: 0.422

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

GnomAD4 genome AF: 0.428 AC: 65102 AN: 152102 Hom.: 15876 Cov.: 32 AF XY: 0.424 AC XY: 31543 AN XY: 74366

Gnomad4 AFR AF: 0.671

Gnomad4 AMR AF: 0.341

Gnomad4 ASJ AF: 0.312

Gnomad4 EAS AF: 0.464

Gnomad4 SAS AF: 0.309

Gnomad4 FIN AF: 0.288

Gnomad4 NFE AF: 0.334

Gnomad4 OTH AF: 0.423

Alfa AF: 0.367 Hom.: 1418

Bravo AF: 0.445

Asia WGS AF: 0.398 AC: 1385 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	5.3
DANN	Benign	0.63

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6903903; hg19: chr6-106577507;