6-106183985-C-T

Variant names:

• chr6-106183985-C-T
• rs10484575
• ENST00000636437.1:c.457+17987G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000636437.1(ATG5):​c.457+17987G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.11 in 152,108 control chromosomes in the GnomAD database, including 1,003 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 0.11 (1003 hom., cov: 32)
• Consequence: ATG5 ENST00000636437.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.757
• Publications: 7 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

ENSG00000303838 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.149 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+17987G>A		intron_variant	Intron 6 of 6	5		ENSP00000490376.1
ATG5	ENST00000636335.1	n.457+17987G>A		intron_variant	Intron 6 of 8	5		ENSP00000490221.1
ENSG00000303838	ENST00000797436.1	n.283+2649C>T		intron_variant	Intron 3 of 3

Frequencies

GnomAD3 genomes AF: 0.110 AC: 16659 AN: 151990 Hom.: 1002 Cov.: 32

Gnomad AFR AF: 0.152

Gnomad AMI AF: 0.0241

Gnomad AMR AF: 0.112

Gnomad ASJ AF: 0.0793

Gnomad EAS AF: 0.0485

Gnomad SAS AF: 0.143

Gnomad FIN AF: 0.0884

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.0919

Gnomad OTH AF: 0.0919

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

GnomAD4 genome AF: 0.110 AC: 16692 AN: 152108 Hom.: 1003 Cov.: 32 AF XY: 0.112 AC XY: 8326 AN XY: 74358

African (AFR) AF: 0.152 AC: 6322 AN: 41504

American (AMR) AF: 0.112 AC: 1715 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0793 AC: 275 AN: 3470

East Asian (EAS) AF: 0.0488 AC: 253 AN: 5182

South Asian (SAS) AF: 0.143 AC: 690 AN: 4820

European-Finnish (FIN) AF: 0.0884 AC: 936 AN: 10588

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 292

European-Non Finnish (NFE) AF: 0.0920 AC: 6247 AN: 67936

Other (OTH) AF: 0.0938 AC: 198 AN: 2112

Alfa AF: 0.0973 Hom.: 3317

Bravo AF: 0.112

Asia WGS AF: 0.135 AC: 470 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.90
DANN	Benign	0.66
PhyloP100		-0.76

Splicing

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

Other links and lift over

dbSNP: rs10484575; hg19: chr6-106631860; COSMIC: COSV58346686; COSMIC: COSV58346686;