rs2303942

Positions:

• chr7-151078219-G-A

Variant summary

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

The NM_006712.5(FASTK):​c.826-127C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.497 in 704,912 control chromosomes in the GnomAD database, including 88,964 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 0.53 (21931 hom., cov: 33)
  • Exomes 𝑓: 0.49 (67033 hom.)
• Consequence: FASTK NM_006712.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.177

Genes affected

FASTK (HGNC:24676): (Fas activated serine/threonine kinase) The protein encoded by this gene is a member of the serine/threonine protein kinase family. This kinase was shown to be activated rapidly during Fas-mediated apoptosis in Jurkat cells. In response to Fas receptor ligation, it phosphorylates TIA1, an apoptosis-promoting nuclear RNA-binding protein. The encoded protein is a strong inducer of lymphocyte apoptosis. Two transcript variants encoding different isoforms have been found for this gene. Other variants exist, but their full-length natures have not yet been determined. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.633 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FASTK	NM_006712.5	c.826-127C>T		intron_variant		ENST00000297532.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FASTK	ENST00000297532.11	c.826-127C>T		intron_variant		1	NM_006712.5	P1

Frequencies

GnomAD3 genomes AF: 0.530 AC: 80589 AN: 151942 Hom.: 21900 Cov.: 33

Gnomad AFR AF: 0.639

Gnomad AMI AF: 0.587

Gnomad AMR AF: 0.573

Gnomad ASJ AF: 0.507

Gnomad EAS AF: 0.426

Gnomad SAS AF: 0.549

Gnomad FIN AF: 0.447

Gnomad MID AF: 0.532

Gnomad NFE AF: 0.475

Gnomad OTH AF: 0.514

GnomAD4 exome AF: 0.488 AC: 269633 AN: 552852 Hom.: 67033 AF XY: 0.490 AC XY: 140705 AN XY: 286970

Gnomad4 AFR exome AF: 0.638

Gnomad4 AMR exome AF: 0.635

Gnomad4 ASJ exome AF: 0.494

Gnomad4 EAS exome AF: 0.427

Gnomad4 SAS exome AF: 0.554

Gnomad4 FIN exome AF: 0.452

Gnomad4 NFE exome AF: 0.473

Gnomad4 OTH exome AF: 0.495

GnomAD4 genome AF: 0.531 AC: 80671 AN: 152060 Hom.: 21931 Cov.: 33 AF XY: 0.530 AC XY: 39416 AN XY: 74318

Gnomad4 AFR AF: 0.639

Gnomad4 AMR AF: 0.573

Gnomad4 ASJ AF: 0.507

Gnomad4 EAS AF: 0.426

Gnomad4 SAS AF: 0.546

Gnomad4 FIN AF: 0.447

Gnomad4 NFE AF: 0.475

Gnomad4 OTH AF: 0.519

Alfa AF: 0.487 Hom.: 21109

Bravo AF: 0.548

Asia WGS AF: 0.523 AC: 1821 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.83
DANN	Benign	0.63
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs2303942; hg19: chr7-150775306; COSMIC: COSV52538936; COSMIC: COSV52538936;