rs9386514

chr6-106189027-T-C

Variant summary

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

The NM_004849.4(ATG5):c.692-2351A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.154 in 152,152 control chromosomes in the GnomAD database, including 2,132 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 0.15 (2132 hom., cov: 32)
• Consequence: ATG5 NM_004849.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.628

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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.197 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATG5	NM_004849.4	c.692-2351A>G		intron_variant		ENST00000369076.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATG5	ENST00000369076.8	c.692-2351A>G		intron_variant		1	NM_004849.4	P1

Frequencies

GnomAD3 genomes AF: 0.155 AC: 23495 AN: 152034 Hom.: 2134 Cov.: 32

Gnomad AFR AF: 0.0760

Gnomad AMI AF: 0.265

Gnomad AMR AF: 0.150

Gnomad ASJ AF: 0.158

Gnomad EAS AF: 0.0471

Gnomad SAS AF: 0.162

Gnomad FIN AF: 0.218

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.200

Gnomad OTH AF: 0.143

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

GnomAD4 genome AF: 0.154 AC: 23490 AN: 152152 Hom.: 2132 Cov.: 32 AF XY: 0.154 AC XY: 11492 AN XY: 74384

Gnomad4 AFR AF: 0.0758

Gnomad4 AMR AF: 0.150

Gnomad4 ASJ AF: 0.158

Gnomad4 EAS AF: 0.0472

Gnomad4 SAS AF: 0.161

Gnomad4 FIN AF: 0.218

Gnomad4 NFE AF: 0.200

Gnomad4 OTH AF: 0.143

Alfa AF: 0.187 Hom.: 1466

Bravo AF: 0.143

Asia WGS AF: 0.0920 AC: 319 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	0.64
Dann	Benign	0.53

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: rs9386514; hg19: chr6-106636902;