rs9551427

Positions:

• chr13-28040603-A-G
• chr13-28040603-A-T

Variant summary

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

The ENST00000241453.12(FLT3):​c.1206-3315T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.662 in 151,900 control chromosomes in the GnomAD database, including 34,339 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 0.66 (34339 hom., cov: 31)
• Consequence: FLT3 ENST00000241453.12 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.374

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.83 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FLT3	NM_004119.3	c.1206-3315T>C		intron_variant		ENST00000241453.12	NP_004110.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FLT3	ENST00000241453.12	c.1206-3315T>C		intron_variant		1	NM_004119.3	ENSP00000241453	P1
FLT3	ENST00000380987.2	c.1206-3315T>C		intron_variant, NMD_transcript_variant		1		ENSP00000370374

Frequencies

GnomAD3 genomes AF: 0.663 AC: 100572 AN: 151782 Hom.: 34319 Cov.: 31

Gnomad AFR AF: 0.486

Gnomad AMI AF: 0.836

Gnomad AMR AF: 0.721

Gnomad ASJ AF: 0.761

Gnomad EAS AF: 0.850

Gnomad SAS AF: 0.847

Gnomad FIN AF: 0.692

Gnomad MID AF: 0.677

Gnomad NFE AF: 0.717

Gnomad OTH AF: 0.683

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.662 AC: 100628 AN: 151900 Hom.: 34339 Cov.: 31 AF XY: 0.667 AC XY: 49481 AN XY: 74232

Gnomad4 AFR AF: 0.485

Gnomad4 AMR AF: 0.722

Gnomad4 ASJ AF: 0.761

Gnomad4 EAS AF: 0.851

Gnomad4 SAS AF: 0.848

Gnomad4 FIN AF: 0.692

Gnomad4 NFE AF: 0.717

Gnomad4 OTH AF: 0.686

Alfa AF: 0.698 Hom.: 7769

Bravo AF: 0.657

Asia WGS AF: 0.772 AC: 2682 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.4
DANN	Benign	0.62

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: rs9551427; hg19: chr13-28614740;