rs11871099

Variant names:

• chr17-37038989-A-G
• rs11871099
• NM_012138.4:c.1619+7304A>G

Variant summary

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

The NM_012138.4(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 NM_012138.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.11
• Publications: 6 publications found

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]

ENSG00000277579 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
AATF	NM_012138.4	c.1619+7304A>G		intron_variant	Intron 11 of 11	ENST00000619387.5	NP_036270.1
AATF	NM_001411094.1	c.1548-17612A>G		intron_variant	Intron 10 of 10		NP_001398023.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AATF	ENST00000619387.5	c.1619+7304A>G		intron_variant	Intron 11 of 11	1	NM_012138.4	ENSP00000477848.1

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

African (AFR) AF: 0.571 AC: 23648 AN: 41450

American (AMR) AF: 0.172 AC: 2624 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.155 AC: 538 AN: 3470

East Asian (EAS) AF: 0.147 AC: 757 AN: 5156

South Asian (SAS) AF: 0.0970 AC: 468 AN: 4826

European-Finnish (FIN) AF: 0.179 AC: 1890 AN: 10582

Middle Eastern (MID) AF: 0.139 AC: 41 AN: 294

European-Non Finnish (NFE) AF: 0.165 AC: 11251 AN: 67990

Other (OTH) AF: 0.207 AC: 437 AN: 2116

Alfa AF: 0.242 Hom.: 6918

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
PhyloP100		-3.1
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: rs11871099; hg19: chr17-35396286;