rs2491222

chr13-28033779-T-Achr13-28033779-T-Cchr13-28033779-T-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.1942+108A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.719 in 864,892 control chromosomes in the GnomAD database, including 230,995 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.63 (33015 hom., cov: 33)
  • Exomes 𝑓: 0.74 (197980 hom.)
• Consequence: FLT3 NM_004119.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.52

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=-0.87).
• BP6: Variant 13-28033779-T-A is Benign according to our data. Variant chr13-28033779-T-A is described in ClinVar as [Benign]. Clinvar id is 1232565.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.767 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FLT3	NM_004119.3	c.1942+108A>T		intron_variant		ENST00000241453.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FLT3	ENST00000241453.12	c.1942+108A>T		intron_variant		1	NM_004119.3	P1
FLT3	ENST00000380987.2	c.1942+108A>T		intron_variant, NMD_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.626 AC: 95240 AN: 152038 Hom.: 33002 Cov.: 33

Gnomad AFR AF: 0.309

Gnomad AMI AF: 0.707

Gnomad AMR AF: 0.664

Gnomad ASJ AF: 0.724

Gnomad EAS AF: 0.726

Gnomad SAS AF: 0.591

Gnomad FIN AF: 0.797

Gnomad MID AF: 0.633

Gnomad NFE AF: 0.773

Gnomad OTH AF: 0.652

GnomAD4 exome AF: 0.738 AC: 526213 AN: 712736 Hom.: 197980 AF XY: 0.733 AC XY: 274222 AN XY: 374064

Gnomad4 AFR exome AF: 0.302

Gnomad4 AMR exome AF: 0.707

Gnomad4 ASJ exome AF: 0.717

Gnomad4 EAS exome AF: 0.684

Gnomad4 SAS exome AF: 0.595

Gnomad4 FIN exome AF: 0.806

Gnomad4 NFE exome AF: 0.777

Gnomad4 OTH exome AF: 0.726

GnomAD4 genome AF: 0.626 AC: 95278 AN: 152156 Hom.: 33015 Cov.: 33 AF XY: 0.625 AC XY: 46529 AN XY: 74398

Gnomad4 AFR AF: 0.309

Gnomad4 AMR AF: 0.665

Gnomad4 ASJ AF: 0.724

Gnomad4 EAS AF: 0.726

Gnomad4 SAS AF: 0.591

Gnomad4 FIN AF: 0.797

Gnomad4 NFE AF: 0.773

Gnomad4 OTH AF: 0.654

Alfa AF: 0.678 Hom.: 4610

Bravo AF: 0.608

Asia WGS AF: 0.639 AC: 2225 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	-0.87
Cadd	Benign	0.71
Dann	Benign	0.35

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: rs2491222; hg19: chr13-28607916; COSMIC: COSV54059632;