6-106189700-C-T

Position:

• chr6-106189700-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004849.4(ATG5):​c.692-3024G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.112 in 150,702 control chromosomes in the GnomAD database, including 1,024 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 (1024 hom., cov: 31)
• Consequence: ATG5 NM_004849.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.233

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.152 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATG5	NM_004849.4	c.692-3024G>A		intron_variant		ENST00000369076.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATG5	ENST00000369076.8	c.692-3024G>A		intron_variant		1	NM_004849.4	P1

Frequencies

GnomAD3 genomes AF: 0.112 AC: 16881 AN: 150614 Hom.: 1023 Cov.: 31

Gnomad AFR AF: 0.155

Gnomad AMI AF: 0.0243

Gnomad AMR AF: 0.114

Gnomad ASJ AF: 0.0793

Gnomad EAS AF: 0.0484

Gnomad SAS AF: 0.157

Gnomad FIN AF: 0.0893

Gnomad MID AF: 0.110

Gnomad NFE AF: 0.0942

Gnomad OTH AF: 0.0962

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

GnomAD4 genome AF: 0.112 AC: 16912 AN: 150702 Hom.: 1024 Cov.: 31 AF XY: 0.115 AC XY: 8435 AN XY: 73554

Gnomad4 AFR AF: 0.155

Gnomad4 AMR AF: 0.114

Gnomad4 ASJ AF: 0.0793

Gnomad4 EAS AF: 0.0487

Gnomad4 SAS AF: 0.157

Gnomad4 FIN AF: 0.0893

Gnomad4 NFE AF: 0.0943

Gnomad4 OTH AF: 0.0981

Alfa AF: 0.105 Hom.: 429

Bravo AF: 0.114

Asia WGS AF: 0.142 AC: 495 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.97
DANN	Benign	0.59

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

Publications

LitVar

Other links and lift over

dbSNP: rs6920944; hg19: chr6-106637575; COSMIC: COSV58346696;