chr13-28053535-C-T

Variant names:

• chr13-28053535-C-T
• rs4769591
• NM_004119.3:c.485-861G>A

Variant summary

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

The NM_004119.3(FLT3):​c.485-861G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.155 in 151,632 control chromosomes in the GnomAD database, including 2,097 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 0.15 (2097 hom., cov: 30)
• Consequence: FLT3 NM_004119.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.131
• Publications: 1 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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.193 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FLT3	NM_004119.3	c.485-861G>A		intron_variant	Intron 4 of 23	ENST00000241453.12	NP_004110.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FLT3	ENST00000241453.12	c.485-861G>A		intron_variant	Intron 4 of 23	1	NM_004119.3	ENSP00000241453.7
FLT3	ENST00000380987.2	n.485-861G>A		intron_variant	Intron 4 of 24	1		ENSP00000370374.2

Frequencies

GnomAD3 genomes AF: 0.155 AC: 23433 AN: 151520 Hom.: 2098 Cov.: 30

Gnomad AFR AF: 0.0800

Gnomad AMI AF: 0.148

Gnomad AMR AF: 0.156

Gnomad ASJ AF: 0.208

Gnomad EAS AF: 0.0483

Gnomad SAS AF: 0.108

Gnomad FIN AF: 0.234

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.196

Gnomad OTH AF: 0.158

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

GnomAD4 genome AF: 0.155 AC: 23434 AN: 151632 Hom.: 2097 Cov.: 30 AF XY: 0.156 AC XY: 11540 AN XY: 74138

African (AFR) AF: 0.0801 AC: 3316 AN: 41380

American (AMR) AF: 0.156 AC: 2378 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.208 AC: 721 AN: 3464

East Asian (EAS) AF: 0.0482 AC: 250 AN: 5184

South Asian (SAS) AF: 0.107 AC: 514 AN: 4800

European-Finnish (FIN) AF: 0.234 AC: 2439 AN: 10404

Middle Eastern (MID) AF: 0.255 AC: 75 AN: 294

European-Non Finnish (NFE) AF: 0.196 AC: 13280 AN: 67866

Other (OTH) AF: 0.156 AC: 327 AN: 2094

Alfa AF: 0.167 Hom.: 308

Bravo AF: 0.145

Asia WGS AF: 0.105 AC: 368 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	5.2
DANN	Benign	0.87
PhyloP100		-0.13
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: rs4769591; hg19: chr13-28627672;