6-106150148-G-A

Variant names:

• chr6-106150148-G-A
• rs1040411
• ENST00000636437.1:c.457+51824C>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+51824C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.472 in 151,748 control chromosomes in the GnomAD database, including 17,415 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 0.47 (17415 hom., cov: 31)
• Consequence: ATG5 ENST00000636437.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.251
• Publications: 15 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.594 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+51824C>T		intron_variant	Intron 6 of 6	5		ENSP00000490376.1
ATG5	ENST00000636335.1	n.457+51824C>T		intron_variant	Intron 6 of 8	5		ENSP00000490221.1

Frequencies

GnomAD3 genomes AF: 0.472 AC: 71593 AN: 151630 Hom.: 17406 Cov.: 31

Gnomad AFR AF: 0.340

Gnomad AMI AF: 0.518

Gnomad AMR AF: 0.555

Gnomad ASJ AF: 0.514

Gnomad EAS AF: 0.611

Gnomad SAS AF: 0.495

Gnomad FIN AF: 0.458

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.521

Gnomad OTH AF: 0.487

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

GnomAD4 genome AF: 0.472 AC: 71637 AN: 151748 Hom.: 17415 Cov.: 31 AF XY: 0.472 AC XY: 34983 AN XY: 74140

African (AFR) AF: 0.340 AC: 14048 AN: 41344

American (AMR) AF: 0.555 AC: 8472 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.514 AC: 1779 AN: 3462

East Asian (EAS) AF: 0.611 AC: 3144 AN: 5142

South Asian (SAS) AF: 0.496 AC: 2383 AN: 4804

European-Finnish (FIN) AF: 0.458 AC: 4812 AN: 10518

Middle Eastern (MID) AF: 0.500 AC: 147 AN: 294

European-Non Finnish (NFE) AF: 0.521 AC: 35349 AN: 67902

Other (OTH) AF: 0.488 AC: 1032 AN: 2114

Alfa AF: 0.510 Hom.: 55981

Bravo AF: 0.477

Asia WGS AF: 0.556 AC: 1933 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.78
DANN	Benign	0.62
PhyloP100		-0.25

Splicing

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

Other links and lift over

dbSNP: rs1040411; hg19: chr6-106598023;