rs11871099

Positions:

• chr17-37038989-A-G

Variant summary

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

The ENST00000619387.5(AATF):​c.1619+7304A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.275 in 152,088 control chromosomes in the GnomAD database, including 8,348 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 0.27 (8348 hom., cov: 32)
• Consequence: AATF ENST00000619387.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.11

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.564 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AATF	NM_012138.4	c.1619+7304A>G		intron_variant		ENST00000619387.5	NP_036270.1
AATF	NM_001411094.1	c.1548-17612A>G		intron_variant			NP_001398023.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AATF	ENST00000619387.5	c.1619+7304A>G		intron_variant		1	NM_012138.4	ENSP00000477848	P2
	ENST00000615419.1	n.178-4030A>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.275 AC: 41737 AN: 151970 Hom.: 8319 Cov.: 32

Gnomad AFR AF: 0.570

Gnomad AMI AF: 0.181

Gnomad AMR AF: 0.171

Gnomad ASJ AF: 0.155

Gnomad EAS AF: 0.147

Gnomad SAS AF: 0.0963

Gnomad FIN AF: 0.179

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.166

Gnomad OTH AF: 0.209

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

GnomAD4 genome AF: 0.275 AC: 41818 AN: 152088 Hom.: 8348 Cov.: 32 AF XY: 0.270 AC XY: 20064 AN XY: 74344

Gnomad4 AFR AF: 0.571

Gnomad4 AMR AF: 0.172

Gnomad4 ASJ AF: 0.155

Gnomad4 EAS AF: 0.147

Gnomad4 SAS AF: 0.0970

Gnomad4 FIN AF: 0.179

Gnomad4 NFE AF: 0.165

Gnomad4 OTH AF: 0.207

Alfa AF: 0.197 Hom.: 2397

Bravo AF: 0.290

Asia WGS AF: 0.145 AC: 506 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	0.0020
DANN	Benign	0.58

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: rs11871099; hg19: chr17-35396286;