rs346081

Positions:

• chr3-11287399-A-G
• chr3-11287399-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001349232.2(ATG7):​c.-11+4961A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.863 in 152,178 control chromosomes in the GnomAD database, including 56,957 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 0.86 (56957 hom., cov: 31)
• Consequence: ATG7 NM_001349232.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.33

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATG7	NM_001349232.2	c.-11+4961A>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.-11+4961A>G		intron_variant			NM_001349232.2	ENSP00000510336.1

Frequencies

GnomAD3 genomes AF: 0.863 AC: 131268 AN: 152060 Hom.: 56898 Cov.: 31

Gnomad AFR AF: 0.911

Gnomad AMI AF: 0.719

Gnomad AMR AF: 0.875

Gnomad ASJ AF: 0.725

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.925

Gnomad FIN AF: 0.888

Gnomad MID AF: 0.796

Gnomad NFE AF: 0.822

Gnomad OTH AF: 0.862

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

GnomAD4 genome AF: 0.863 AC: 131388 AN: 152178 Hom.: 56957 Cov.: 31 AF XY: 0.867 AC XY: 64518 AN XY: 74386

Gnomad4 AFR AF: 0.911

Gnomad4 AMR AF: 0.875

Gnomad4 ASJ AF: 0.725

Gnomad4 EAS AF: 0.999

Gnomad4 SAS AF: 0.925

Gnomad4 FIN AF: 0.888

Gnomad4 NFE AF: 0.822

Gnomad4 OTH AF: 0.864

Alfa AF: 0.850 Hom.: 7664

Bravo AF: 0.866

Asia WGS AF: 0.958 AC: 3332 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.044
DANN	Benign	0.64

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: rs346081; hg19: chr3-11329085;