chr15-90894158-A-T

Position:

• chr15-90894158-A-T

Variant summary

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

The NM_002005.4(FES):​c.2326+100A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.298 in 1,380,082 control chromosomes in the GnomAD database, including 63,915 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 (5935 hom., cov: 33)
  • Exomes 𝑓: 0.30 (57980 hom.)
• Consequence: FES NM_002005.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.735

Genes affected

FES (HGNC:3657): (FES proto-oncogene, tyrosine kinase) This gene encodes the human cellular counterpart of a feline sarcoma retrovirus protein with transforming capabilities. The gene product has tyrosine-specific protein kinase activity and that activity is required for maintenance of cellular transformation. Its chromosomal location has linked it to a specific translocation event identified in patients with acute promyelocytic leukemia but it is also involved in normal hematopoiesis as well as growth factor and cytokine receptor signaling. Alternative splicing results in multiple variants encoding different isoforms.[provided by RefSeq, Jan 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.319 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FES	NM_002005.4	c.2326+100A>T		intron_variant		ENST00000328850.8	NP_001996.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FES	ENST00000328850.8	c.2326+100A>T		intron_variant		1	NM_002005.4	ENSP00000331504	P1

Frequencies

GnomAD3 genomes AF: 0.274 AC: 41608 AN: 152040 Hom.: 5931 Cov.: 33

Gnomad AFR AF: 0.234

Gnomad AMI AF: 0.283

Gnomad AMR AF: 0.228

Gnomad ASJ AF: 0.350

Gnomad EAS AF: 0.104

Gnomad SAS AF: 0.237

Gnomad FIN AF: 0.252

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.323

Gnomad OTH AF: 0.275

GnomAD4 exome AF: 0.301 AC: 369233 AN: 1227924 Hom.: 57980 AF XY: 0.301 AC XY: 183997 AN XY: 611820

Gnomad4 AFR exome AF: 0.232

Gnomad4 AMR exome AF: 0.155

Gnomad4 ASJ exome AF: 0.352

Gnomad4 EAS exome AF: 0.103

Gnomad4 SAS exome AF: 0.249

Gnomad4 FIN exome AF: 0.264

Gnomad4 NFE exome AF: 0.322

Gnomad4 OTH exome AF: 0.284

GnomAD4 genome AF: 0.274 AC: 41631 AN: 152158 Hom.: 5935 Cov.: 33 AF XY: 0.268 AC XY: 19952 AN XY: 74380

Gnomad4 AFR AF: 0.234

Gnomad4 AMR AF: 0.227

Gnomad4 ASJ AF: 0.350

Gnomad4 EAS AF: 0.105

Gnomad4 SAS AF: 0.237

Gnomad4 FIN AF: 0.252

Gnomad4 NFE AF: 0.323

Gnomad4 OTH AF: 0.274

Alfa AF: 0.181 Hom.: 411

Bravo AF: 0.267

Asia WGS AF: 0.183 AC: 637 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	1.7
DANN	Benign	0.69

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2521501; hg19: chr15-91437388; COSMIC: COSV60998584; COSMIC: COSV60998584;