13-28003551-G-T

Position:

• chr13-28003551-G-T

Variant summary

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

The NM_004119.3(FLT3):​c.*501C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.473 in 236,966 control chromosomes in the GnomAD database, including 27,140 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 0.46 (16557 hom., cov: 32)
  • Exomes 𝑓: 0.50 (10583 hom.)
• Consequence: FLT3 NM_004119.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.79

Genes affected

FLT3 (HGNC:3765): (fms related receptor tyrosine kinase 3) This gene encodes a class III receptor tyrosine kinase that regulates hematopoiesis. This receptor is activated by binding of the fms-related tyrosine kinase 3 ligand to the extracellular domain, which induces homodimer formation in the plasma membrane leading to autophosphorylation of the receptor. The activated receptor kinase subsequently phosphorylates and activates multiple cytoplasmic effector molecules in pathways involved in apoptosis, proliferation, and differentiation of hematopoietic cells in bone marrow. Mutations that result in the constitutive activation of this receptor result in acute myeloid leukemia and acute lymphoblastic leukemia. [provided by RefSeq, Jan 2015]

FLT3 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.612 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FLT3	NM_004119.3	c.*501C>A		3_prime_UTR_variant	24/24	ENST00000241453.12	NP_004110.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FLT3	ENST00000241453	c.*501C>A		3_prime_UTR_variant	24/24	1	NM_004119.3	ENSP00000241453.7

Frequencies

GnomAD3 genomes AF: 0.460 AC: 69821 AN: 151824 Hom.: 16548 Cov.: 32

Gnomad AFR AF: 0.369

Gnomad AMI AF: 0.474

Gnomad AMR AF: 0.453

Gnomad ASJ AF: 0.500

Gnomad EAS AF: 0.502

Gnomad SAS AF: 0.631

Gnomad FIN AF: 0.436

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.503

Gnomad OTH AF: 0.483

GnomAD4 exome AF: 0.497 AC: 42286 AN: 85024 Hom.: 10583 Cov.: 0 AF XY: 0.497 AC XY: 19601 AN XY: 39422

Gnomad4 AFR exome AF: 0.374

Gnomad4 AMR exome AF: 0.431

Gnomad4 ASJ exome AF: 0.491

Gnomad4 EAS exome AF: 0.550

Gnomad4 SAS exome AF: 0.598

Gnomad4 FIN exome AF: 0.455

Gnomad4 NFE exome AF: 0.500

Gnomad4 OTH exome AF: 0.490

GnomAD4 genome AF: 0.460 AC: 69858 AN: 151942 Hom.: 16557 Cov.: 32 AF XY: 0.460 AC XY: 34166 AN XY: 74264

Gnomad4 AFR AF: 0.368

Gnomad4 AMR AF: 0.453

Gnomad4 ASJ AF: 0.500

Gnomad4 EAS AF: 0.503

Gnomad4 SAS AF: 0.631

Gnomad4 FIN AF: 0.436

Gnomad4 NFE AF: 0.503

Gnomad4 OTH AF: 0.486

Alfa AF: 0.499 Hom.: 39441

Bravo AF: 0.457

Asia WGS AF: 0.554 AC: 1925 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	6.1
DANN	Benign	0.58

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

Publications

LitVar

Other links and lift over

dbSNP: rs3829382; hg19: chr13-28577688;