rs12110990

Positions:

• chr6-106156261-G-A
• chr6-106156261-G-T

Variant summary

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

The ENST00000636437.1(ATG5):​c.457+45711C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0762 in 151,854 control chromosomes in the GnomAD database, including 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 0.076 (887 hom., cov: 31)
• Consequence: ATG5 ENST00000636437.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0990

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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.196 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATG5	ENST00000636437.1	c.457+45711C>T		intron_variant		5		ENSP00000490376
ATG5	ENST00000636335.1	c.457+45711C>T		intron_variant, NMD_transcript_variant		5		ENSP00000490221

Frequencies

GnomAD3 genomes AF: 0.0760 AC: 11527 AN: 151736 Hom.: 874 Cov.: 31

Gnomad AFR AF: 0.199

Gnomad AMI AF: 0.0527

Gnomad AMR AF: 0.0368

Gnomad ASJ AF: 0.0435

Gnomad EAS AF: 0.105

Gnomad SAS AF: 0.0489

Gnomad FIN AF: 0.0121

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0219

Gnomad OTH AF: 0.0614

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

GnomAD4 genome AF: 0.0762 AC: 11577 AN: 151854 Hom.: 887 Cov.: 31 AF XY: 0.0738 AC XY: 5476 AN XY: 74214

Gnomad4 AFR AF: 0.200

Gnomad4 AMR AF: 0.0367

Gnomad4 ASJ AF: 0.0435

Gnomad4 EAS AF: 0.104

Gnomad4 SAS AF: 0.0500

Gnomad4 FIN AF: 0.0121

Gnomad4 NFE AF: 0.0219

Gnomad4 OTH AF: 0.0613

Alfa AF: 0.0289 Hom.: 125

Bravo AF: 0.0832

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.1
DANN	Benign	0.64

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs12110990; hg19: chr6-106604136; COSMIC: COSV60263689;