rs2245214

Variant names:

• chr6-106214866-C-G
• rs2245214
• NM_004849.4:c.574-12777G>C

Variant summary

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

The NM_004849.4(ATG5):​c.574-12777G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.418 in 151,862 control chromosomes in the GnomAD database, including 13,513 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 0.42 (13513 hom., cov: 32)
• Consequence: ATG5 NM_004849.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0200
• Publications: 41 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.509 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004849.4. 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
	ATG5	NM_004849.4	MANE Select	c.574-12777G>C		intron	N/A	NP_004840.1	A9UGY9
	ATG5	NM_001286106.2		c.574-12777G>C		intron	N/A	NP_001273035.1	Q9H1Y0-1
	ATG5	NM_001286108.2		c.570-12777G>C		intron	N/A	NP_001273037.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATG5	ENST00000369076.8	TSL:1 MANE Select	c.574-12777G>C		intron	N/A	ENSP00000358072.3	Q9H1Y0-1
	ATG5	ENST00000343245.7	TSL:1	c.574-12777G>C		intron	N/A	ENSP00000343313.3	Q9H1Y0-1
	ATG5	ENST00000635758.2	TSL:1	c.340-12777G>C		intron	N/A	ENSP00000490493.1	Q9H1Y0-2

Frequencies

GnomAD3 genomes AF: 0.418 AC: 63361 AN: 151744 Hom.: 13478 Cov.: 32

Gnomad AFR AF: 0.464

Gnomad AMI AF: 0.334

Gnomad AMR AF: 0.518

Gnomad ASJ AF: 0.364

Gnomad EAS AF: 0.482

Gnomad SAS AF: 0.371

Gnomad FIN AF: 0.391

Gnomad MID AF: 0.312

Gnomad NFE AF: 0.374

Gnomad OTH AF: 0.405

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

GnomAD4 genome AF: 0.418 AC: 63455 AN: 151862 Hom.: 13513 Cov.: 32 AF XY: 0.422 AC XY: 31283 AN XY: 74202

African (AFR) AF: 0.465 AC: 19247 AN: 41404

American (AMR) AF: 0.519 AC: 7921 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.364 AC: 1261 AN: 3466

East Asian (EAS) AF: 0.483 AC: 2489 AN: 5158

South Asian (SAS) AF: 0.370 AC: 1779 AN: 4810

European-Finnish (FIN) AF: 0.391 AC: 4117 AN: 10536

Middle Eastern (MID) AF: 0.318 AC: 93 AN: 292

European-Non Finnish (NFE) AF: 0.374 AC: 25395 AN: 67910

Other (OTH) AF: 0.404 AC: 852 AN: 2110

Alfa AF: 0.402 Hom.: 1552

Bravo AF: 0.434

Asia WGS AF: 0.432 AC: 1500 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.78
DANN	Benign	0.29
PhyloP100		0.020
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: rs2245214; hg19: chr6-106662741;