rs9372120

Positions:

• chr6-106219660-T-G

Variant summary

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

The NM_004849.4(ATG5):​c.574-17571A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.155 in 152,072 control chromosomes in the GnomAD database, including 2,178 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 0.16 (2178 hom., cov: 32)
• Consequence: ATG5 NM_004849.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.176

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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.2 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATG5	NM_004849.4	c.574-17571A>C		intron_variant		ENST00000369076.8	NP_004840.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATG5	ENST00000369076.8	c.574-17571A>C		intron_variant		1	NM_004849.4	ENSP00000358072	P1

Frequencies

GnomAD3 genomes AF: 0.156 AC: 23629 AN: 151954 Hom.: 2180 Cov.: 32

Gnomad AFR AF: 0.0729

Gnomad AMI AF: 0.266

Gnomad AMR AF: 0.152

Gnomad ASJ AF: 0.161

Gnomad EAS AF: 0.0473

Gnomad SAS AF: 0.163

Gnomad FIN AF: 0.220

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.203

Gnomad OTH AF: 0.147

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

GnomAD4 genome AF: 0.155 AC: 23624 AN: 152072 Hom.: 2178 Cov.: 32 AF XY: 0.155 AC XY: 11541 AN XY: 74332

Gnomad4 AFR AF: 0.0727

Gnomad4 AMR AF: 0.152

Gnomad4 ASJ AF: 0.161

Gnomad4 EAS AF: 0.0475

Gnomad4 SAS AF: 0.162

Gnomad4 FIN AF: 0.220

Gnomad4 NFE AF: 0.203

Gnomad4 OTH AF: 0.147

Alfa AF: 0.183 Hom.: 564

Bravo AF: 0.144

Asia WGS AF: 0.0920 AC: 320 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.4
DANN	Benign	0.65

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: rs9372120; hg19: chr6-106667535;