chr3-11517628-G-C

Variant names:

• chr3-11517628-G-C
• rs17536147
• NM_001349232.2:c.2080-37183G>C

Variant summary

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

The NM_001349232.2(ATG7):​c.2080-37183G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0505 in 152,320 control chromosomes in the GnomAD database, including 264 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 0.050 (264 hom., cov: 32)
• Consequence: ATG7 NM_001349232.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.257
• Publications: 4 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: Labcorp Genetics (formerly Invitae), G2P, ClinGen, Ambry Genetics

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.076 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATG7	NM_001349232.2	c.2080-37183G>C		intron_variant	Intron 20 of 20	ENST00000693202.1	NP_001336161.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATG7	ENST00000693202.1	c.2080-37183G>C		intron_variant	Intron 20 of 20		NM_001349232.2	ENSP00000510336.1

Frequencies

GnomAD3 genomes AF: 0.0505 AC: 7689 AN: 152202 Hom.: 264 Cov.: 32

Gnomad AFR AF: 0.0132

Gnomad AMI AF: 0.102

Gnomad AMR AF: 0.0480

Gnomad ASJ AF: 0.0876

Gnomad EAS AF: 0.000962

Gnomad SAS AF: 0.0176

Gnomad FIN AF: 0.0443

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.0778

Gnomad OTH AF: 0.0626

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

GnomAD4 genome AF: 0.0505 AC: 7689 AN: 152320 Hom.: 264 Cov.: 32 AF XY: 0.0476 AC XY: 3548 AN XY: 74486

African (AFR) AF: 0.0132 AC: 547 AN: 41574

American (AMR) AF: 0.0479 AC: 733 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0876 AC: 304 AN: 3472

East Asian (EAS) AF: 0.000964 AC: 5 AN: 5188

South Asian (SAS) AF: 0.0180 AC: 87 AN: 4828

European-Finnish (FIN) AF: 0.0443 AC: 470 AN: 10616

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.0778 AC: 5289 AN: 68024

Other (OTH) AF: 0.0615 AC: 130 AN: 2114

Alfa AF: 0.0343 Hom.: 27

Bravo AF: 0.0512

Asia WGS AF: 0.00895 AC: 31 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	6.8
DANN	Benign	0.77
PhyloP100		0.26
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: rs17536147; hg19: chr3-11559102;