rs12212740

Variant names:

• chr6-106301433-G-A
• rs12212740
• NM_004849.4:c.236+6931C>T

Variant summary

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

The NM_004849.4(ATG5):​c.236+6931C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0842 in 152,012 control chromosomes in the GnomAD database, including 744 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 0.084 (744 hom., cov: 32)
• Consequence: ATG5 NM_004849.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.656
• Publications: 18 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.116 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATG5	NM_004849.4	c.236+6931C>T		intron_variant	Intron 3 of 7	ENST00000369076.8	NP_004840.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATG5	ENST00000369076.8	c.236+6931C>T		intron_variant	Intron 3 of 7	1	NM_004849.4	ENSP00000358072.3

Frequencies

GnomAD3 genomes AF: 0.0843 AC: 12809 AN: 151894 Hom.: 744 Cov.: 32

Gnomad AFR AF: 0.0239

Gnomad AMI AF: 0.272

Gnomad AMR AF: 0.0727

Gnomad ASJ AF: 0.216

Gnomad EAS AF: 0.0801

Gnomad SAS AF: 0.0568

Gnomad FIN AF: 0.0674

Gnomad MID AF: 0.162

Gnomad NFE AF: 0.118

Gnomad OTH AF: 0.112

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

GnomAD4 genome AF: 0.0842 AC: 12797 AN: 152012 Hom.: 744 Cov.: 32 AF XY: 0.0805 AC XY: 5978 AN XY: 74290

African (AFR) AF: 0.0238 AC: 988 AN: 41530

American (AMR) AF: 0.0726 AC: 1109 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.216 AC: 747 AN: 3466

East Asian (EAS) AF: 0.0799 AC: 414 AN: 5182

South Asian (SAS) AF: 0.0564 AC: 272 AN: 4820

European-Finnish (FIN) AF: 0.0674 AC: 714 AN: 10588

Middle Eastern (MID) AF: 0.161 AC: 47 AN: 292

European-Non Finnish (NFE) AF: 0.118 AC: 8024 AN: 67838

Other (OTH) AF: 0.111 AC: 234 AN: 2112

Alfa AF: 0.114 Hom.: 1825

Bravo AF: 0.0841

Asia WGS AF: 0.0660 AC: 229 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	1.1
DANN	Benign	0.79
PhyloP100		-0.66
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: rs12212740; hg19: chr6-106749308;