6-106129111-T-C

Variant names:

• chr6-106129111-T-C
• rs7761791
• ENST00000636437.1:c.457+72861A>G

Variant summary

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

The ENST00000636437.1(ATG5):​c.457+72861A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.428 in 151,748 control chromosomes in the GnomAD database, including 15,842 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 0.43 (15842 hom., cov: 31)
• Consequence: ATG5 ENST00000636437.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.456
• 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: Ambry Genetics, Labcorp Genetics (formerly Invitae), ClinGen

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.664 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000636437.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATG5	ENST00000636437.1	TSL:5	c.457+72861A>G		intron	N/A	ENSP00000490376.1	A0A1B0GV54
	ATG5	ENST00000636335.1	TSL:5	n.458-50796A>G		intron	N/A	ENSP00000490221.1	A0A1B0GUS1

Frequencies

GnomAD3 genomes AF: 0.428 AC: 64854 AN: 151632 Hom.: 15790 Cov.: 31

Gnomad AFR AF: 0.670

Gnomad AMI AF: 0.373

Gnomad AMR AF: 0.341

Gnomad ASJ AF: 0.311

Gnomad EAS AF: 0.465

Gnomad SAS AF: 0.308

Gnomad FIN AF: 0.287

Gnomad MID AF: 0.386

Gnomad NFE AF: 0.334

Gnomad OTH AF: 0.423

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

GnomAD4 genome AF: 0.428 AC: 64972 AN: 151748 Hom.: 15842 Cov.: 31 AF XY: 0.424 AC XY: 31475 AN XY: 74162

African (AFR) AF: 0.671 AC: 27752 AN: 41372

American (AMR) AF: 0.341 AC: 5199 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.311 AC: 1079 AN: 3468

East Asian (EAS) AF: 0.467 AC: 2395 AN: 5132

South Asian (SAS) AF: 0.309 AC: 1482 AN: 4790

European-Finnish (FIN) AF: 0.287 AC: 3026 AN: 10552

Middle Eastern (MID) AF: 0.381 AC: 112 AN: 294

European-Non Finnish (NFE) AF: 0.334 AC: 22697 AN: 67870

Other (OTH) AF: 0.424 AC: 891 AN: 2102

Alfa AF: 0.363 Hom.: 45362

Bravo AF: 0.444

Asia WGS AF: 0.398 AC: 1385 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.3
DANN	Benign	0.37
PhyloP100		-0.46

Splicing

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

Other links and lift over

dbSNP: rs7761791; hg19: chr6-106576986;