rs2442794

Variant names:

• chr3-11509527-A-G
• rs2442794
• NM_001349232.2:c.2080-45284A>G

Variant summary

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

The NM_001349232.2(ATG7):​c.2080-45284A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.732 in 151,936 control chromosomes in the GnomAD database, including 41,636 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 0.73 (41636 hom., cov: 31)
• Consequence: ATG7 NM_001349232.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.583
• Publications: 5 publications found

Genes affected

ATG7 (HGNC:16935): (autophagy related 7) This gene encodes an E1-like activating enzyme that is essential for autophagy and cytoplasmic to vacuole transport. The encoded protein is also thought to modulate p53-dependent cell cycle pathways during prolonged metabolic stress. It has been associated with multiple functions, including axon membrane trafficking, axonal homeostasis, mitophagy, adipose differentiation, and hematopoietic stem cell maintenance. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2015]

ATG7 Gene-Disease associations (from GenCC):

• spinocerebellar ataxia, autosomal recessive 31

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: Ambry Genetics, ClinGen, G2P, Labcorp Genetics (formerly Invitae)

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 (EAS) allele frequency at 95% confidence interval = 0.951 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001349232.2. 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
	ATG7	NM_001349232.2	MANE Select	c.2080-45284A>G		intron	N/A	NP_001336161.1
	ATG7	NM_001349233.2		c.2080-45284A>G		intron	N/A	NP_001336162.1
	ATG7	NM_001349234.2		c.2080-45284A>G		intron	N/A	NP_001336163.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATG7	ENST00000693202.1	MANE Select	c.2080-45284A>G		intron	N/A	ENSP00000510336.1
	ATG7	ENST00000354449.7	TSL:1	c.2080-45284A>G		intron	N/A	ENSP00000346437.3
	ATG7	ENST00000354956.9	TSL:1	c.1999-45284A>G		intron	N/A	ENSP00000347042.5

Frequencies

GnomAD3 genomes AF: 0.732 AC: 111135 AN: 151818 Hom.: 41596 Cov.: 31

Gnomad AFR AF: 0.575

Gnomad AMI AF: 0.596

Gnomad AMR AF: 0.786

Gnomad ASJ AF: 0.686

Gnomad EAS AF: 0.973

Gnomad SAS AF: 0.854

Gnomad FIN AF: 0.869

Gnomad MID AF: 0.690

Gnomad NFE AF: 0.771

Gnomad OTH AF: 0.735

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

GnomAD4 genome AF: 0.732 AC: 111235 AN: 151936 Hom.: 41636 Cov.: 31 AF XY: 0.740 AC XY: 54980 AN XY: 74290

African (AFR) AF: 0.576 AC: 23813 AN: 41360

American (AMR) AF: 0.786 AC: 11990 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.686 AC: 2381 AN: 3470

East Asian (EAS) AF: 0.973 AC: 5043 AN: 5182

South Asian (SAS) AF: 0.855 AC: 4124 AN: 4824

European-Finnish (FIN) AF: 0.869 AC: 9187 AN: 10574

Middle Eastern (MID) AF: 0.697 AC: 205 AN: 294

European-Non Finnish (NFE) AF: 0.771 AC: 52403 AN: 67964

Other (OTH) AF: 0.734 AC: 1548 AN: 2108

Alfa AF: 0.760 Hom.: 21285

Bravo AF: 0.719

Asia WGS AF: 0.865 AC: 3005 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	3.8
DANN	Benign	0.81
PhyloP100		-0.58
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: rs2442794; hg19: chr3-11551001;