rs4946730

Variant names:

• chr6-106165216-G-A
• rs4946730
• ENST00000636437.1:c.457+36756C>T

Your query was ambiguous. Multiple possible variants found:

• chr6-106165216-G-A
• chr6-106165216-G-C

Variant summary

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

The ENST00000636437.1(ATG5):​c.457+36756C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.307 in 151,938 control chromosomes in the GnomAD database, including 7,906 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 0.31 (7906 hom., cov: 31)
• Consequence: ATG5 ENST00000636437.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.605
• Publications: 6 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 = 0.455 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

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

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATG5	ENST00000636437.1	TSL:5	c.457+36756C>T		intron	N/A	ENSP00000490376.1
	ATG5	ENST00000636335.1	TSL:5	n.457+36756C>T		intron	N/A	ENSP00000490221.1
	ENSG00000303838	ENST00000797436.1		n.33+510G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.306 AC: 46524 AN: 151820 Hom.: 7872 Cov.: 31

Gnomad AFR AF: 0.460

Gnomad AMI AF: 0.265

Gnomad AMR AF: 0.258

Gnomad ASJ AF: 0.290

Gnomad EAS AF: 0.354

Gnomad SAS AF: 0.213

Gnomad FIN AF: 0.204

Gnomad MID AF: 0.304

Gnomad NFE AF: 0.244

Gnomad OTH AF: 0.302

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

GnomAD4 genome AF: 0.307 AC: 46626 AN: 151938 Hom.: 7906 Cov.: 31 AF XY: 0.303 AC XY: 22463 AN XY: 74242

African (AFR) AF: 0.461 AC: 19089 AN: 41420

American (AMR) AF: 0.258 AC: 3936 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.290 AC: 1006 AN: 3472

East Asian (EAS) AF: 0.355 AC: 1828 AN: 5156

South Asian (SAS) AF: 0.214 AC: 1028 AN: 4802

European-Finnish (FIN) AF: 0.204 AC: 2147 AN: 10538

Middle Eastern (MID) AF: 0.306 AC: 90 AN: 294

European-Non Finnish (NFE) AF: 0.244 AC: 16618 AN: 67978

Other (OTH) AF: 0.306 AC: 643 AN: 2102

Alfa AF: 0.267 Hom.: 25508

Bravo AF: 0.319

Asia WGS AF: 0.297 AC: 1034 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.21
DANN	Benign	0.16
PhyloP100		-0.60

Splicing

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

Other links and lift over

dbSNP: rs4946730; hg19: chr6-106613091; COSMIC: COSV60263713;