13-28015130-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_004119.3(FLT3):c.2753+27G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.491 in 1,419,534 control chromosomes in the GnomAD database, including 175,492 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.45 (16540 hom., cov: 32)
  • Exomes 𝑓: 0.50 (158952 hom.)
• Consequence: FLT3 NM_004119.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.272

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 13-28015130-C-T is Benign according to our data. Variant chr13-28015130-C-T is described in ClinVar as [Benign]. Clinvar id is 1243109.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.518 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FLT3	NM_004119.3	c.2753+27G>A		intron_variant		ENST00000241453.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FLT3	ENST00000241453.12	c.2753+27G>A		intron_variant		1	NM_004119.3	P1
FLT3	ENST00000380987.2	c.*665+27G>A		intron_variant, NMD_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.451 AC: 68393 AN: 151814 Hom.: 16540 Cov.: 32

Gnomad AFR AF: 0.290

Gnomad AMI AF: 0.553

Gnomad AMR AF: 0.501

Gnomad ASJ AF: 0.485

Gnomad EAS AF: 0.413

Gnomad SAS AF: 0.312

Gnomad FIN AF: 0.604

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.523

Gnomad OTH AF: 0.440

GnomAD3 exomes AF: 0.477 AC: 108782 AN: 228208 Hom.: 26752 AF XY: 0.472 AC XY: 58172 AN XY: 123192

Gnomad AFR exome AF: 0.290

Gnomad AMR exome AF: 0.524

Gnomad ASJ exome AF: 0.493

Gnomad EAS exome AF: 0.407

Gnomad SAS exome AF: 0.328

Gnomad FIN exome AF: 0.595

Gnomad NFE exome AF: 0.517

Gnomad OTH exome AF: 0.478

GnomAD4 exome AF: 0.496 AC: 628549 AN: 1267602 Hom.: 158952 Cov.: 17 AF XY: 0.491 AC XY: 314010 AN XY: 639024

Gnomad4 AFR exome AF: 0.284

Gnomad4 AMR exome AF: 0.523

Gnomad4 ASJ exome AF: 0.489

Gnomad4 EAS exome AF: 0.400

Gnomad4 SAS exome AF: 0.332

Gnomad4 FIN exome AF: 0.588

Gnomad4 NFE exome AF: 0.516

Gnomad4 OTH exome AF: 0.475

GnomAD4 genome AF: 0.450 AC: 68416 AN: 151932 Hom.: 16540 Cov.: 32 AF XY: 0.454 AC XY: 33679 AN XY: 74240

Gnomad4 AFR AF: 0.290

Gnomad4 AMR AF: 0.501

Gnomad4 ASJ AF: 0.485

Gnomad4 EAS AF: 0.412

Gnomad4 SAS AF: 0.312

Gnomad4 FIN AF: 0.604

Gnomad4 NFE AF: 0.523

Gnomad4 OTH AF: 0.437

Alfa AF: 0.484 Hom.: 3827

Bravo AF: 0.436

Asia WGS AF: 0.340 AC: 1183 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 11, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
Cadd	Benign	8.9
Dann	Benign	0.79

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: rs4073630; hg19: chr13-28589267; COSMIC: COSV54044770; COSMIC: COSV54044770;