7-151078219-G-A

Variant names:

• chr7-151078219-G-A
• rs2303942
• NM_006712.5:c.826-127C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 9 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006712.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FASTK	NM_006712.5	MANE Select	c.826-127C>T		intron	N/A	NP_006703.1	A0A090N8Z7
	FASTK	NM_001258461.2		c.745-127C>T		intron	N/A	NP_001245390.1	Q14296-3
	FASTK	NM_033015.4		c.403-127C>T		intron	N/A	NP_148936.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FASTK	ENST00000297532.11	TSL:1 MANE Select	c.826-127C>T		intron	N/A	ENSP00000297532.6	Q14296-1
	FASTK	ENST00000482571.2	TSL:1	c.745-127C>T		intron	N/A	ENSP00000418516.1	Q14296-3
	FASTK	ENST00000353841.6	TSL:1	c.403-127C>T		intron	N/A	ENSP00000324817.6	Q14296-2

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

African (AFR) AF: 0.638 AC: 9160 AN: 14354

American (AMR) AF: 0.635 AC: 11951 AN: 18826

Ashkenazi Jewish (ASJ) AF: 0.494 AC: 7054 AN: 14280

East Asian (EAS) AF: 0.427 AC: 13552 AN: 31708

South Asian (SAS) AF: 0.554 AC: 26861 AN: 48528

European-Finnish (FIN) AF: 0.452 AC: 17304 AN: 38242

Middle Eastern (MID) AF: 0.514 AC: 1367 AN: 2660

European-Non Finnish (NFE) AF: 0.473 AC: 167892 AN: 354950

Other (OTH) AF: 0.495 AC: 14492 AN: 29304

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

African (AFR) AF: 0.639 AC: 26529 AN: 41504

American (AMR) AF: 0.573 AC: 8763 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.507 AC: 1758 AN: 3468

East Asian (EAS) AF: 0.426 AC: 2199 AN: 5168

South Asian (SAS) AF: 0.546 AC: 2630 AN: 4814

European-Finnish (FIN) AF: 0.447 AC: 4715 AN: 10554

Middle Eastern (MID) AF: 0.524 AC: 154 AN: 294

European-Non Finnish (NFE) AF: 0.475 AC: 32291 AN: 67954

Other (OTH) AF: 0.519 AC: 1097 AN: 2112

Alfa AF: 0.495 Hom.: 27892

Bravo AF: 0.548

Asia WGS AF: 0.523 AC: 1821 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.83
DANN	Benign	0.63
PhyloP100		-0.18
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2303942; hg19: chr7-150775306; COSMIC: COSV52538936; COSMIC: COSV52538936;