rs2442794

Positions:

• chr3-11509527-A-G

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATG7	NM_001349232.2	c.2080-45284A>G		intron_variant		ENST00000693202.1	NP_001336161.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATG7	ENST00000693202.1	c.2080-45284A>G		intron_variant			NM_001349232.2	ENSP00000510336	P1

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

Gnomad4 AFR AF: 0.576

Gnomad4 AMR AF: 0.786

Gnomad4 ASJ AF: 0.686

Gnomad4 EAS AF: 0.973

Gnomad4 SAS AF: 0.855

Gnomad4 FIN AF: 0.869

Gnomad4 NFE AF: 0.771

Gnomad4 OTH AF: 0.734

Alfa AF: 0.762 Hom.: 18954

Bravo AF: 0.719

Asia WGS AF: 0.865 AC: 3005 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	3.8
DANN	Benign	0.81

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

Publications

LitVar

Other links and lift over

dbSNP: rs2442794; hg19: chr3-11551001;