rs7220048

Variant names:

• chr17-81144773-T-C
• rs7220048
• NM_001080395.3:c.56-10272A>G

Variant summary

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

The NM_001080395.3(AATK):​c.56-10272A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.488 in 152,144 control chromosomes in the GnomAD database, including 18,471 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 0.49 (18471 hom., cov: 34)
• Consequence: AATK NM_001080395.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.53
• Publications: 14 publications found

Genes affected

AATK (HGNC:21): (apoptosis associated tyrosine kinase) The protein encoded by this gene contains a tyrosine kinase domain at the N-terminus and a proline-rich domain at the C-terminus. This gene is induced during apoptosis, and expression of this gene may be a necessary pre-requisite for the induction of growth arrest and/or apoptosis of myeloid precursor cells. This gene has been shown to produce neuronal differentiation in a neuroblastoma cell line. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jun 2011]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.55 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AATK	NM_001080395.3	c.56-10272A>G		intron_variant	Intron 1 of 13	ENST00000326724.9	NP_001073864.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AATK	ENST00000326724.9	c.56-10272A>G		intron_variant	Intron 1 of 13	5	NM_001080395.3	ENSP00000324196.4
AATK	ENST00000374792.6	n.56-10272A>G		intron_variant	Intron 1 of 15	2		ENSP00000363924.2
AATK	ENST00000572798.1	n.274-10272A>G		intron_variant	Intron 2 of 2	2

Frequencies

GnomAD3 genomes AF: 0.488 AC: 74224 AN: 152026 Hom.: 18454 Cov.: 34

Gnomad AFR AF: 0.556

Gnomad AMI AF: 0.646

Gnomad AMR AF: 0.473

Gnomad ASJ AF: 0.411

Gnomad EAS AF: 0.286

Gnomad SAS AF: 0.327

Gnomad FIN AF: 0.460

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.484

Gnomad OTH AF: 0.474

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

GnomAD4 genome AF: 0.488 AC: 74279 AN: 152144 Hom.: 18471 Cov.: 34 AF XY: 0.482 AC XY: 35836 AN XY: 74374

African (AFR) AF: 0.556 AC: 23077 AN: 41488

American (AMR) AF: 0.472 AC: 7224 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.411 AC: 1425 AN: 3470

East Asian (EAS) AF: 0.287 AC: 1482 AN: 5170

South Asian (SAS) AF: 0.327 AC: 1577 AN: 4828

European-Finnish (FIN) AF: 0.460 AC: 4868 AN: 10584

Middle Eastern (MID) AF: 0.463 AC: 136 AN: 294

European-Non Finnish (NFE) AF: 0.484 AC: 32912 AN: 67988

Other (OTH) AF: 0.467 AC: 989 AN: 2116

Alfa AF: 0.482 Hom.: 63433

Bravo AF: 0.495

Asia WGS AF: 0.288 AC: 1002 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.41
DANN	Benign	0.38
PhyloP100		-1.5
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: rs7220048; hg19: chr17-79118573;