13-28015358-C-G

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.2654-102G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.363 in 857,866 control chromosomes in the GnomAD database, including 61,629 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.32 (8728 hom., cov: 30)
  • Exomes 𝑓: 0.37 (52901 hom.)
• Consequence: FLT3 NM_004119.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.612

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=-0.82).
• BP6: Variant 13-28015358-C-G is Benign according to our data. Variant chr13-28015358-C-G is described in ClinVar as [Benign]. Clinvar id is 1283726.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.426 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FLT3	NM_004119.3	c.2654-102G>C		intron_variant		ENST00000241453.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FLT3	ENST00000241453.12	c.2654-102G>C		intron_variant		1	NM_004119.3	P1
FLT3	ENST00000380987.2	c.*566-102G>C		intron_variant, NMD_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.316 AC: 47995 AN: 151836 Hom.: 8725 Cov.: 30

Gnomad AFR AF: 0.155

Gnomad AMI AF: 0.405

Gnomad AMR AF: 0.291

Gnomad ASJ AF: 0.433

Gnomad EAS AF: 0.161

Gnomad SAS AF: 0.227

Gnomad FIN AF: 0.304

Gnomad MID AF: 0.405

Gnomad NFE AF: 0.430

Gnomad OTH AF: 0.368

GnomAD4 exome AF: 0.373 AC: 263296 AN: 705910 Hom.: 52901 AF XY: 0.369 AC XY: 137894 AN XY: 373240

Gnomad4 AFR exome AF: 0.152

Gnomad4 AMR exome AF: 0.245

Gnomad4 ASJ exome AF: 0.440

Gnomad4 EAS exome AF: 0.154

Gnomad4 SAS exome AF: 0.243

Gnomad4 FIN exome AF: 0.317

Gnomad4 NFE exome AF: 0.429

Gnomad4 OTH exome AF: 0.369

GnomAD4 genome AF: 0.316 AC: 47989 AN: 151956 Hom.: 8728 Cov.: 30 AF XY: 0.307 AC XY: 22776 AN XY: 74258

Gnomad4 AFR AF: 0.155

Gnomad4 AMR AF: 0.290

Gnomad4 ASJ AF: 0.433

Gnomad4 EAS AF: 0.161

Gnomad4 SAS AF: 0.228

Gnomad4 FIN AF: 0.304

Gnomad4 NFE AF: 0.430

Gnomad4 OTH AF: 0.365

Alfa AF: 0.370 Hom.: 1391

Bravo AF: 0.306

Asia WGS AF: 0.193 AC: 672 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

Jun 18, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	5.3
Dann	Benign	0.46

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: rs9579142; hg19: chr13-28589495; COSMIC: COSV54054966; COSMIC: COSV54054966;