rs2306658

Variant names:

• chr17-36949012-G-C
• rs2306658
• NM_012138.4:c.-114G>C

Your query was ambiguous. Multiple possible variants found:

• chr17-36949012-G-C
• chr17-36949012-G-T

Variant summary

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

The NM_012138.4(AATF):​c.-114G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.504 in 1,029,984 control chromosomes in the GnomAD database, including 141,271 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 0.40 (15163 hom., cov: 35)
  • Exomes 𝑓: 0.52 (126108 hom.)
• Consequence: AATF NM_012138.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.709
• Publications: 13 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.563 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012138.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AATF	NM_012138.4	MANE Select	c.-114G>C		5_prime_UTR	Exon 1 of 12	NP_036270.1
	AATF	NM_001411094.1		c.-114G>C		5_prime_UTR	Exon 1 of 11	NP_001398023.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AATF	ENST00000619387.5	TSL:1 MANE Select	c.-114G>C		5_prime_UTR	Exon 1 of 12	ENSP00000477848.1
	AATF	ENST00000679508.1		n.88G>C		non_coding_transcript_exon	Exon 1 of 9
	AATF	ENST00000679985.1		n.88G>C		non_coding_transcript_exon	Exon 1 of 8

Frequencies

GnomAD3 genomes AF: 0.399 AC: 60664 AN: 152116 Hom.: 15175 Cov.: 35

Gnomad AFR AF: 0.109

Gnomad AMI AF: 0.541

Gnomad AMR AF: 0.333

Gnomad ASJ AF: 0.590

Gnomad EAS AF: 0.192

Gnomad SAS AF: 0.400

Gnomad FIN AF: 0.555

Gnomad MID AF: 0.589

Gnomad NFE AF: 0.568

Gnomad OTH AF: 0.440

GnomAD4 exome AF: 0.523 AC: 458882 AN: 877750 Hom.: 126108 Cov.: 12 AF XY: 0.522 AC XY: 230283 AN XY: 441242

African (AFR) AF: 0.100 AC: 2042 AN: 20398

American (AMR) AF: 0.268 AC: 7947 AN: 29702

Ashkenazi Jewish (ASJ) AF: 0.583 AC: 10576 AN: 18138

East Asian (EAS) AF: 0.220 AC: 7048 AN: 31990

South Asian (SAS) AF: 0.413 AC: 24902 AN: 60344

European-Finnish (FIN) AF: 0.540 AC: 19008 AN: 35194

Middle Eastern (MID) AF: 0.572 AC: 2529 AN: 4422

European-Non Finnish (NFE) AF: 0.573 AC: 365031 AN: 637336

Other (OTH) AF: 0.492 AC: 19799 AN: 40226

GnomAD4 genome AF: 0.398 AC: 60632 AN: 152234 Hom.: 15163 Cov.: 35 AF XY: 0.394 AC XY: 29324 AN XY: 74420

African (AFR) AF: 0.109 AC: 4510 AN: 41564

American (AMR) AF: 0.333 AC: 5090 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.590 AC: 2044 AN: 3466

East Asian (EAS) AF: 0.191 AC: 987 AN: 5168

South Asian (SAS) AF: 0.399 AC: 1927 AN: 4828

European-Finnish (FIN) AF: 0.555 AC: 5876 AN: 10596

Middle Eastern (MID) AF: 0.578 AC: 170 AN: 294

European-Non Finnish (NFE) AF: 0.568 AC: 38621 AN: 68002

Other (OTH) AF: 0.434 AC: 916 AN: 2112

Alfa AF: 0.362 Hom.: 1117

Bravo AF: 0.370

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	4.3
DANN	Benign	0.45
PhyloP100		-0.71
PromoterAI		0.033	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Mutation Taster		=300/0	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: rs2306658; hg19: chr17-35306312;