rs665791

Positions:

• chr6-106226975-G-A
• chr6-106226975-G-C
• chr6-106226975-G-T

Variant summary

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

The NM_004849.4(ATG5):​c.573+21175C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.593 in 151,734 control chromosomes in the GnomAD database, including 27,741 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 0.59 (27741 hom., cov: 30)
• Consequence: ATG5 NM_004849.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.830

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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.759 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATG5	NM_004849.4	c.573+21175C>T		intron_variant		ENST00000369076.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATG5	ENST00000369076.8	c.573+21175C>T		intron_variant		1	NM_004849.4	P1

Frequencies

GnomAD3 genomes AF: 0.592 AC: 89832 AN: 151616 Hom.: 27678 Cov.: 30

Gnomad AFR AF: 0.765

Gnomad AMI AF: 0.437

Gnomad AMR AF: 0.648

Gnomad ASJ AF: 0.476

Gnomad EAS AF: 0.566

Gnomad SAS AF: 0.511

Gnomad FIN AF: 0.510

Gnomad MID AF: 0.433

Gnomad NFE AF: 0.505

Gnomad OTH AF: 0.562

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

GnomAD4 genome AF: 0.593 AC: 89965 AN: 151734 Hom.: 27741 Cov.: 30 AF XY: 0.595 AC XY: 44119 AN XY: 74142

Gnomad4 AFR AF: 0.766

Gnomad4 AMR AF: 0.649

Gnomad4 ASJ AF: 0.476

Gnomad4 EAS AF: 0.567

Gnomad4 SAS AF: 0.510

Gnomad4 FIN AF: 0.510

Gnomad4 NFE AF: 0.505

Gnomad4 OTH AF: 0.566

Alfa AF: 0.531 Hom.: 19351

Bravo AF: 0.611

Asia WGS AF: 0.584 AC: 2027 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.90
DANN	Benign	0.45

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: rs665791; hg19: chr6-106674850;