rs9551427

Variant names:

• chr13-28040603-A-G
• rs9551427
• NM_004119.3:c.1206-3315T>C

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004119.3(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 NM_004119.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.374
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004119.3. 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
	FLT3	NM_004119.3	MANE Select	c.1206-3315T>C		intron	N/A	NP_004110.2	P36888-1
	FLT3	NR_130706.2		n.1272-3315T>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FLT3	ENST00000241453.12	TSL:1 MANE Select	c.1206-3315T>C		intron	N/A	ENSP00000241453.7	P36888-1
	FLT3	ENST00000380987.2	TSL:1	n.1206-3315T>C		intron	N/A	ENSP00000370374.2	E7ER61
	FLT3	ENST00000864668.1		c.485-4560T>C		intron	N/A	ENSP00000534727.1

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

African (AFR) AF: 0.485 AC: 20064 AN: 41334

American (AMR) AF: 0.722 AC: 11022 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.761 AC: 2642 AN: 3472

East Asian (EAS) AF: 0.851 AC: 4399 AN: 5172

South Asian (SAS) AF: 0.848 AC: 4087 AN: 4820

European-Finnish (FIN) AF: 0.692 AC: 7288 AN: 10532

Middle Eastern (MID) AF: 0.670 AC: 197 AN: 294

European-Non Finnish (NFE) AF: 0.717 AC: 48719 AN: 67982

Other (OTH) AF: 0.686 AC: 1448 AN: 2110

Alfa AF: 0.694 Hom.: 12779

Bravo AF: 0.657

Asia WGS AF: 0.772 AC: 2682 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.4
DANN	Benign	0.62
PhyloP100		-0.37
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs9551427; hg19: chr13-28614740;