chr6-106237320-G-C

Variant names:

• chr6-106237320-G-C
• rs3827644
• NM_004849.4:c.573+10830C>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.573+10830C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.153 in 152,018 control chromosomes in the GnomAD database, including 2,118 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 (2118 hom., cov: 32)
• Consequence: ATG5 NM_004849.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0630
• Publications: 15 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=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.195 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATG5	NM_004849.4	c.573+10830C>G		intron_variant	Intron 6 of 7	ENST00000369076.8	NP_004840.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATG5	ENST00000369076.8	c.573+10830C>G		intron_variant	Intron 6 of 7	1	NM_004849.4	ENSP00000358072.3

Frequencies

GnomAD3 genomes AF: 0.153 AC: 23206 AN: 151900 Hom.: 2120 Cov.: 32

Gnomad AFR AF: 0.0720

Gnomad AMI AF: 0.264

Gnomad AMR AF: 0.150

Gnomad ASJ AF: 0.161

Gnomad EAS AF: 0.0468

Gnomad SAS AF: 0.162

Gnomad FIN AF: 0.220

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.198

Gnomad OTH AF: 0.145

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

GnomAD4 genome AF: 0.153 AC: 23201 AN: 152018 Hom.: 2118 Cov.: 32 AF XY: 0.153 AC XY: 11364 AN XY: 74290

African (AFR) AF: 0.0718 AC: 2977 AN: 41468

American (AMR) AF: 0.150 AC: 2294 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.161 AC: 558 AN: 3470

East Asian (EAS) AF: 0.0469 AC: 243 AN: 5180

South Asian (SAS) AF: 0.161 AC: 775 AN: 4820

European-Finnish (FIN) AF: 0.220 AC: 2317 AN: 10532

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

European-Non Finnish (NFE) AF: 0.198 AC: 13470 AN: 67952

Other (OTH) AF: 0.145 AC: 306 AN: 2116

Alfa AF: 0.174 Hom.: 322

Bravo AF: 0.141

Asia WGS AF: 0.0900 AC: 313 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.9
DANN	Benign	0.59
PhyloP100		0.063
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: rs3827644; hg19: chr6-106685195; COSMIC: COSV58350012;