rs12110990

Variant names:

• chr6-106156261-G-A
• rs12110990
• ENST00000636437.1:c.457+45711C>T

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 publications found

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 Gene-Disease associations (from GenCC):

• spinocerebellar ataxia, autosomal recessive 25

  Inheritance: AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, ClinGen

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATG5	ENST00000636437.1	c.457+45711C>T		intron_variant	Intron 6 of 6	5		ENSP00000490376.1
ATG5	ENST00000636335.1	n.457+45711C>T		intron_variant	Intron 6 of 8	5		ENSP00000490221.1

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

African (AFR) AF: 0.200 AC: 8277 AN: 41376

American (AMR) AF: 0.0367 AC: 560 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.0435 AC: 151 AN: 3472

East Asian (EAS) AF: 0.104 AC: 539 AN: 5174

South Asian (SAS) AF: 0.0500 AC: 241 AN: 4818

European-Finnish (FIN) AF: 0.0121 AC: 127 AN: 10530

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.0219 AC: 1486 AN: 67920

Other (OTH) AF: 0.0613 AC: 129 AN: 2106

Alfa AF: 0.0368 Hom.: 279

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
PhyloP100		0.099

Splicing

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

Other links and lift over

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