rs66520040

Positions:

• chr13-28032094-G-A
• chr13-28032094-G-C

Variant summary

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

The NM_004119.3(FLT3):​c.1942+1793C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.152 in 152,050 control chromosomes in the GnomAD database, including 3,662 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 (3662 hom., cov: 32)
• Consequence: FLT3 NM_004119.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.92

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.397 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FLT3	NM_004119.3	c.1942+1793C>T		intron_variant		ENST00000241453.12	NP_004110.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FLT3	ENST00000241453.12	c.1942+1793C>T		intron_variant		1	NM_004119.3	ENSP00000241453	P1
FLT3	ENST00000380987.2	c.1942+1793C>T		intron_variant, NMD_transcript_variant		1		ENSP00000370374

Frequencies

GnomAD3 genomes AF: 0.152 AC: 23102 AN: 151932 Hom.: 3651 Cov.: 32

Gnomad AFR AF: 0.402

Gnomad AMI AF: 0.0186

Gnomad AMR AF: 0.0738

Gnomad ASJ AF: 0.0746

Gnomad EAS AF: 0.151

Gnomad SAS AF: 0.196

Gnomad FIN AF: 0.0387

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.0396

Gnomad OTH AF: 0.111

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

GnomAD4 genome AF: 0.152 AC: 23148 AN: 152050 Hom.: 3662 Cov.: 32 AF XY: 0.152 AC XY: 11318 AN XY: 74338

Gnomad4 AFR AF: 0.402

Gnomad4 AMR AF: 0.0737

Gnomad4 ASJ AF: 0.0746

Gnomad4 EAS AF: 0.151

Gnomad4 SAS AF: 0.195

Gnomad4 FIN AF: 0.0387

Gnomad4 NFE AF: 0.0396

Gnomad4 OTH AF: 0.112

Alfa AF: 0.111 Hom.: 505

Bravo AF: 0.163

Asia WGS AF: 0.173 AC: 603 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.37
DANN	Benign	0.53

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: rs66520040; hg19: chr13-28606231;