rs3829382

Variant names:

• chr13-28003551-G-T
• rs3829382
• NM_004119.3:c.*501C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004119.3(FLT3):​c.*501C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.473 in 236,966 control chromosomes in the GnomAD database, including 27,140 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.46 (16557 hom., cov: 32)
  • Exomes 𝑓: 0.50 (10583 hom.)
• Consequence: FLT3 NM_004119.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.79
• Publications: 17 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.612 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004119.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FLT3	NM_004119.3	MANE Select	c.*501C>A		3_prime_UTR	Exon 24 of 24	NP_004110.2	P36888-1
	FLT3	NR_130706.2		n.3681C>A		non_coding_transcript_exon	Exon 25 of 25

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FLT3	ENST00000241453.12	TSL:1 MANE Select	c.*501C>A		3_prime_UTR	Exon 24 of 24	ENSP00000241453.7	P36888-1
	FLT3	ENST00000864668.1		c.*501C>A		3_prime_UTR	Exon 18 of 18	ENSP00000534727.1
	FLT3	ENST00000380987.2	TSL:1	n.*1395C>A		downstream_gene	N/A	ENSP00000370374.2	E7ER61

Frequencies

GnomAD3 genomes AF: 0.460 AC: 69821 AN: 151824 Hom.: 16548 Cov.: 32

Gnomad AFR AF: 0.369

Gnomad AMI AF: 0.474

Gnomad AMR AF: 0.453

Gnomad ASJ AF: 0.500

Gnomad EAS AF: 0.502

Gnomad SAS AF: 0.631

Gnomad FIN AF: 0.436

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.503

Gnomad OTH AF: 0.483

GnomAD4 exome AF: 0.497 AC: 42286 AN: 85024 Hom.: 10583 Cov.: 0 AF XY: 0.497 AC XY: 19601 AN XY: 39422

African (AFR) AF: 0.374 AC: 1465 AN: 3920

American (AMR) AF: 0.431 AC: 1452 AN: 3370

Ashkenazi Jewish (ASJ) AF: 0.491 AC: 2530 AN: 5156

East Asian (EAS) AF: 0.550 AC: 6407 AN: 11654

South Asian (SAS) AF: 0.598 AC: 614 AN: 1026

European-Finnish (FIN) AF: 0.455 AC: 225 AN: 494

Middle Eastern (MID) AF: 0.437 AC: 215 AN: 492

European-Non Finnish (NFE) AF: 0.500 AC: 26013 AN: 52044

Other (OTH) AF: 0.490 AC: 3365 AN: 6868

GnomAD4 genome AF: 0.460 AC: 69858 AN: 151942 Hom.: 16557 Cov.: 32 AF XY: 0.460 AC XY: 34166 AN XY: 74264

African (AFR) AF: 0.368 AC: 15256 AN: 41432

American (AMR) AF: 0.453 AC: 6905 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.500 AC: 1735 AN: 3470

East Asian (EAS) AF: 0.503 AC: 2594 AN: 5156

South Asian (SAS) AF: 0.631 AC: 3030 AN: 4802

European-Finnish (FIN) AF: 0.436 AC: 4607 AN: 10570

Middle Eastern (MID) AF: 0.398 AC: 117 AN: 294

European-Non Finnish (NFE) AF: 0.503 AC: 34164 AN: 67954

Other (OTH) AF: 0.486 AC: 1021 AN: 2102

Alfa AF: 0.496 Hom.: 77594

Bravo AF: 0.457

Asia WGS AF: 0.554 AC: 1925 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	6.1
DANN	Benign	0.58
PhyloP100		1.8
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3829382; hg19: chr13-28577688;