13-28015525-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.2653+65G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.86 (54770 hom., cov: 18)
  • Exomes 𝑓: 0.98 (305091 hom.)
  • Failed GnomAD Quality Control
• Consequence: FLT3 NM_004119.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -4.17

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=-0.91).
• BP6: Variant 13-28015525-C-G is Benign according to our data. Variant chr13-28015525-C-G is described in ClinVar as [Benign]. Clinvar id is 1256865.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.991 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FLT3	NM_004119.3	c.2653+65G>C		intron_variant		ENST00000241453.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FLT3	ENST00000241453.12	c.2653+65G>C		intron_variant		1	NM_004119.3	P1
FLT3	ENST00000380987.2	c.*565+65G>C		intron_variant, NMD_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.858 AC: 120244 AN: 140088 Hom.: 54756 Cov.: 18

Gnomad AFR AF: 0.517

Gnomad AMI AF: 0.999

Gnomad AMR AF: 0.924

Gnomad ASJ AF: 0.997

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.994

Gnomad FIN AF: 0.999

Gnomad MID AF: 0.891

Gnomad NFE AF: 0.997

Gnomad OTH AF: 0.893

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.981 AC: 617662 AN: 629680 Hom.: 305091 AF XY: 0.984 AC XY: 334172 AN XY: 339622

Gnomad4 AFR exome AF: 0.510

Gnomad4 AMR exome AF: 0.968

Gnomad4 ASJ exome AF: 0.997

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 0.998

Gnomad4 FIN exome AF: 0.999

Gnomad4 NFE exome AF: 0.997

Gnomad4 OTH exome AF: 0.961

GnomAD4 genome AF: 0.858 AC: 120302 AN: 140208 Hom.: 54770 Cov.: 18 AF XY: 0.859 AC XY: 57733 AN XY: 67184

Gnomad4 AFR AF: 0.517

Gnomad4 AMR AF: 0.924

Gnomad4 ASJ AF: 0.997

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 0.995

Gnomad4 FIN AF: 0.999

Gnomad4 NFE AF: 0.997

Gnomad4 OTH AF: 0.894

Alfa AF: 0.871 Hom.: 2259

Bravo AF: 0.841

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	-0.91
Cadd	Benign	1.3
Dann	Benign	0.29

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs4497507; hg19: chr13-28589662;