rs2245214

Positions:

• chr6-106214866-C-G

Variant summary

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

The NM_004849.4(ATG5):​c.574-12777G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.418 in 151,862 control chromosomes in the GnomAD database, including 13,513 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 0.42 (13513 hom., cov: 32)
• Consequence: ATG5 NM_004849.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0200

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.509 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATG5	NM_004849.4	c.574-12777G>C		intron_variant		ENST00000369076.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATG5	ENST00000369076.8	c.574-12777G>C		intron_variant		1	NM_004849.4	P1

Frequencies

GnomAD3 genomes AF: 0.418 AC: 63361 AN: 151744 Hom.: 13478 Cov.: 32

Gnomad AFR AF: 0.464

Gnomad AMI AF: 0.334

Gnomad AMR AF: 0.518

Gnomad ASJ AF: 0.364

Gnomad EAS AF: 0.482

Gnomad SAS AF: 0.371

Gnomad FIN AF: 0.391

Gnomad MID AF: 0.312

Gnomad NFE AF: 0.374

Gnomad OTH AF: 0.405

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

GnomAD4 genome AF: 0.418 AC: 63455 AN: 151862 Hom.: 13513 Cov.: 32 AF XY: 0.422 AC XY: 31283 AN XY: 74202

Gnomad4 AFR AF: 0.465

Gnomad4 AMR AF: 0.519

Gnomad4 ASJ AF: 0.364

Gnomad4 EAS AF: 0.483

Gnomad4 SAS AF: 0.370

Gnomad4 FIN AF: 0.391

Gnomad4 NFE AF: 0.374

Gnomad4 OTH AF: 0.404

Alfa AF: 0.402 Hom.: 1552

Bravo AF: 0.434

Asia WGS AF: 0.432 AC: 1500 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.78
DANN	Benign	0.29

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs2245214; hg19: chr6-106662741;