17-36973537-A-G

Position:

• chr17-36973537-A-G

Variant summary

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

The NM_012138.4(AATF):​c.833-13080A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.22 in 152,136 control chromosomes in the GnomAD database, including 4,747 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 0.22 (4747 hom., cov: 32)
• Consequence: AATF NM_012138.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.182

Genes affected

AATF (HGNC:19235): (apoptosis antagonizing transcription factor) The protein encoded by this gene was identified on the basis of its interaction with MAP3K12/DLK, a protein kinase known to be involved in the induction of cell apoptosis. This gene product contains a leucine zipper, which is a characteristic motif of transcription factors, and was shown to exhibit strong transactivation activity when fused to Gal4 DNA binding domain. Overexpression of this gene interfered with MAP3K12 induced apoptosis. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.31 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AATF	NM_012138.4	c.833-13080A>G		intron_variant		ENST00000619387.5
AATF	NM_001411094.1	c.833-13080A>G		intron_variant
AATF	XM_047435748.1	c.833-14982A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AATF	ENST00000619387.5	c.833-13080A>G		intron_variant		1	NM_012138.4	P2

Frequencies

GnomAD3 genomes AF: 0.220 AC: 33422 AN: 152018 Hom.: 4751 Cov.: 32

Gnomad AFR AF: 0.0545

Gnomad AMI AF: 0.408

Gnomad AMR AF: 0.207

Gnomad ASJ AF: 0.386

Gnomad EAS AF: 0.0406

Gnomad SAS AF: 0.214

Gnomad FIN AF: 0.286

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.314

Gnomad OTH AF: 0.272

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

GnomAD4 genome AF: 0.220 AC: 33407 AN: 152136 Hom.: 4747 Cov.: 32 AF XY: 0.217 AC XY: 16121 AN XY: 74386

Gnomad4 AFR AF: 0.0544

Gnomad4 AMR AF: 0.207

Gnomad4 ASJ AF: 0.386

Gnomad4 EAS AF: 0.0405

Gnomad4 SAS AF: 0.214

Gnomad4 FIN AF: 0.286

Gnomad4 NFE AF: 0.314

Gnomad4 OTH AF: 0.269

Alfa AF: 0.286 Hom.: 4043

Bravo AF: 0.204

Asia WGS AF: 0.139 AC: 486 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	10
DANN	Benign	0.88

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: rs1564796; hg19: chr17-35330836;