13-28015372-C-T

Position:

• chr13-28015372-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_004119.3(FLT3):​c.2654-116G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.343 in 794,854 control chromosomes in the GnomAD database, including 50,939 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.30 (7988 hom., cov: 30)
  • Exomes 𝑓: 0.35 (42951 hom.)
• Consequence: FLT3 NM_004119.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.00

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP6: Variant 13-28015372-C-T is Benign according to our data. Variant chr13-28015372-C-T is described in ClinVar as [Benign]. Clinvar id is 1277163.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.408 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FLT3	NM_004119.3	c.2654-116G>A		intron_variant		ENST00000241453.12	NP_004110.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FLT3	ENST00000241453.12	c.2654-116G>A		intron_variant		1	NM_004119.3	ENSP00000241453.7
FLT3	ENST00000380987.2	n.*566-116G>A		intron_variant		1		ENSP00000370374.2

Frequencies

GnomAD3 genomes AF: 0.303 AC: 46027 AN: 151682 Hom.: 7984 Cov.: 30

Gnomad AFR AF: 0.152

Gnomad AMI AF: 0.400

Gnomad AMR AF: 0.282

Gnomad ASJ AF: 0.415

Gnomad EAS AF: 0.151

Gnomad SAS AF: 0.215

Gnomad FIN AF: 0.289

Gnomad MID AF: 0.377

Gnomad NFE AF: 0.412

Gnomad OTH AF: 0.350

GnomAD4 exome AF: 0.352 AC: 226371 AN: 643052 Hom.: 42951 AF XY: 0.348 AC XY: 119393 AN XY: 342790

Gnomad4 AFR exome AF: 0.151

Gnomad4 AMR exome AF: 0.245

Gnomad4 ASJ exome AF: 0.419

Gnomad4 EAS exome AF: 0.152

Gnomad4 SAS exome AF: 0.231

Gnomad4 FIN exome AF: 0.301

Gnomad4 NFE exome AF: 0.406

Gnomad4 OTH exome AF: 0.352

GnomAD4 genome AF: 0.303 AC: 46028 AN: 151802 Hom.: 7988 Cov.: 30 AF XY: 0.295 AC XY: 21866 AN XY: 74186

Gnomad4 AFR AF: 0.152

Gnomad4 AMR AF: 0.282

Gnomad4 ASJ AF: 0.415

Gnomad4 EAS AF: 0.151

Gnomad4 SAS AF: 0.216

Gnomad4 FIN AF: 0.289

Gnomad4 NFE AF: 0.412

Gnomad4 OTH AF: 0.348

Alfa AF: 0.388 Hom.: 11380

Bravo AF: 0.295

Asia WGS AF: 0.187 AC: 652 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 18, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.63
DANN	Benign	0.78

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: rs9579143; hg19: chr13-28589509;