rs1766208

Positions:

• chr6-106305574-C-T

Variant summary

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

The NM_004849.4(ATG5):​c.236+2790G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.213 in 152,138 control chromosomes in the GnomAD database, including 3,887 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 0.21 (3887 hom., cov: 32)
• Consequence: ATG5 NM_004849.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0870

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.337 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATG5	NM_004849.4	c.236+2790G>A		intron_variant		ENST00000369076.8	NP_004840.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATG5	ENST00000369076.8	c.236+2790G>A		intron_variant		1	NM_004849.4	ENSP00000358072.3

Frequencies

GnomAD3 genomes AF: 0.213 AC: 32403 AN: 152020 Hom.: 3868 Cov.: 32

Gnomad AFR AF: 0.267

Gnomad AMI AF: 0.0680

Gnomad AMR AF: 0.344

Gnomad ASJ AF: 0.202

Gnomad EAS AF: 0.190

Gnomad SAS AF: 0.194

Gnomad FIN AF: 0.139

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.168

Gnomad OTH AF: 0.217

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

GnomAD4 genome AF: 0.213 AC: 32480 AN: 152138 Hom.: 3887 Cov.: 32 AF XY: 0.216 AC XY: 16097 AN XY: 74378

Gnomad4 AFR AF: 0.267

Gnomad4 AMR AF: 0.345

Gnomad4 ASJ AF: 0.202

Gnomad4 EAS AF: 0.191

Gnomad4 SAS AF: 0.194

Gnomad4 FIN AF: 0.139

Gnomad4 NFE AF: 0.168

Gnomad4 OTH AF: 0.217

Alfa AF: 0.192 Hom.: 2386

Bravo AF: 0.236

Asia WGS AF: 0.225 AC: 784 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.4
DANN	Benign	0.75

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: rs1766208; hg19: chr6-106753449; COSMIC: COSV58347008; COSMIC: COSV58347008;