chr15-90894158-A-T

Variant names:

• chr15-90894158-A-T
• rs2521501
• NM_002005.4:c.2326+100A>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 114 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002005.4. 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
	FES	NM_002005.4	MANE Select	c.2326+100A>T		intron	N/A	NP_001996.1
	FES	NM_001143783.1		c.2152+100A>T		intron	N/A	NP_001137255.1
	FES	NM_001143784.1		c.2116+100A>T		intron	N/A	NP_001137256.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FES	ENST00000328850.8	TSL:1 MANE Select	c.2326+100A>T		intron	N/A	ENSP00000331504.3
	FES	ENST00000394300.7	TSL:1	c.2152+100A>T		intron	N/A	ENSP00000377837.3
	FES	ENST00000444422.2	TSL:1	c.2116+100A>T		intron	N/A	ENSP00000400868.2

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

African (AFR) AF: 0.232 AC: 6524 AN: 28156

American (AMR) AF: 0.155 AC: 5496 AN: 35540

Ashkenazi Jewish (ASJ) AF: 0.352 AC: 7300 AN: 20758

East Asian (EAS) AF: 0.103 AC: 3950 AN: 38312

South Asian (SAS) AF: 0.249 AC: 17961 AN: 72164

European-Finnish (FIN) AF: 0.264 AC: 10434 AN: 39594

Middle Eastern (MID) AF: 0.315 AC: 1627 AN: 5172

European-Non Finnish (NFE) AF: 0.322 AC: 301139 AN: 936082

Other (OTH) AF: 0.284 AC: 14802 AN: 52146

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

African (AFR) AF: 0.234 AC: 9710 AN: 41482

American (AMR) AF: 0.227 AC: 3477 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.350 AC: 1216 AN: 3470

East Asian (EAS) AF: 0.105 AC: 542 AN: 5182

South Asian (SAS) AF: 0.237 AC: 1143 AN: 4832

European-Finnish (FIN) AF: 0.252 AC: 2671 AN: 10602

Middle Eastern (MID) AF: 0.259 AC: 76 AN: 294

European-Non Finnish (NFE) AF: 0.323 AC: 21961 AN: 67986

Other (OTH) AF: 0.274 AC: 579 AN: 2112

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	1.7
DANN	Benign	0.69
PhyloP100		0.73
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2521501; hg19: chr15-91437388; COSMIC: COSV60998584; COSMIC: COSV60998584;