rs9386514

Variant names:

• chr6-106189027-T-C
• rs9386514
• NM_004849.4:c.692-2351A>G

Variant summary

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

The NM_004849.4(ATG5):​c.692-2351A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.154 in 152,152 control chromosomes in the GnomAD database, including 2,132 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 0.15 (2132 hom., cov: 32)
• Consequence: ATG5 NM_004849.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.628
• Publications: 11 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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.197 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATG5	NM_004849.4	c.692-2351A>G		intron_variant	Intron 7 of 7	ENST00000369076.8	NP_004840.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATG5	ENST00000369076.8	c.692-2351A>G		intron_variant	Intron 7 of 7	1	NM_004849.4	ENSP00000358072.3

Frequencies

GnomAD3 genomes AF: 0.155 AC: 23495 AN: 152034 Hom.: 2134 Cov.: 32

Gnomad AFR AF: 0.0760

Gnomad AMI AF: 0.265

Gnomad AMR AF: 0.150

Gnomad ASJ AF: 0.158

Gnomad EAS AF: 0.0471

Gnomad SAS AF: 0.162

Gnomad FIN AF: 0.218

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.200

Gnomad OTH AF: 0.143

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

GnomAD4 genome AF: 0.154 AC: 23490 AN: 152152 Hom.: 2132 Cov.: 32 AF XY: 0.154 AC XY: 11492 AN XY: 74384

African (AFR) AF: 0.0758 AC: 3147 AN: 41516

American (AMR) AF: 0.150 AC: 2290 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.158 AC: 549 AN: 3472

East Asian (EAS) AF: 0.0472 AC: 245 AN: 5190

South Asian (SAS) AF: 0.161 AC: 777 AN: 4828

European-Finnish (FIN) AF: 0.218 AC: 2302 AN: 10562

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.200 AC: 13615 AN: 67978

Other (OTH) AF: 0.143 AC: 302 AN: 2112

Alfa AF: 0.186 Hom.: 2292

Bravo AF: 0.143

Asia WGS AF: 0.0920 AC: 319 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.64
DANN	Benign	0.53
PhyloP100		-0.63
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs9386514; hg19: chr6-106636902;