3-11302077-C-A

Variant names:

• chr3-11302077-C-A
• rs11706903
• NM_001349232.2:c.215+2661C>A

Variant summary

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

The NM_001349232.2(ATG7):​c.215+2661C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.204 in 152,100 control chromosomes in the GnomAD database, including 3,559 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 0.20 (3559 hom., cov: 32)
• Consequence: ATG7 NM_001349232.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.01
• 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

ENSG00000294152 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.341 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATG7	NM_001349232.2	c.215+2661C>A		intron_variant	Intron 5 of 20	ENST00000693202.1	NP_001336161.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATG7	ENST00000693202.1	c.215+2661C>A		intron_variant	Intron 5 of 20		NM_001349232.2	ENSP00000510336.1

Frequencies

GnomAD3 genomes AF: 0.204 AC: 31052 AN: 151980 Hom.: 3551 Cov.: 32

Gnomad AFR AF: 0.189

Gnomad AMI AF: 0.0581

Gnomad AMR AF: 0.333

Gnomad ASJ AF: 0.193

Gnomad EAS AF: 0.297

Gnomad SAS AF: 0.353

Gnomad FIN AF: 0.286

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.157

Gnomad OTH AF: 0.208

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

GnomAD4 genome AF: 0.204 AC: 31095 AN: 152100 Hom.: 3559 Cov.: 32 AF XY: 0.215 AC XY: 16001 AN XY: 74318

African (AFR) AF: 0.190 AC: 7864 AN: 41496

American (AMR) AF: 0.333 AC: 5088 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.193 AC: 670 AN: 3470

East Asian (EAS) AF: 0.297 AC: 1538 AN: 5172

South Asian (SAS) AF: 0.355 AC: 1713 AN: 4826

European-Finnish (FIN) AF: 0.286 AC: 3024 AN: 10574

Middle Eastern (MID) AF: 0.194 AC: 57 AN: 294

European-Non Finnish (NFE) AF: 0.157 AC: 10654 AN: 67972

Other (OTH) AF: 0.205 AC: 434 AN: 2114

Alfa AF: 0.183 Hom.: 362

Bravo AF: 0.206

Asia WGS AF: 0.306 AC: 1061 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.1
DANN	Benign	0.53
PhyloP100		-1.0
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: rs11706903; hg19: chr3-11343551;