chr13-28015372-C-T

Variant names:

• chr13-28015372-C-T
• rs9579143
• NM_004119.3:c.2654-116G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_004119.3(FLT3):​c.2654-116G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.343 in 794,854 control chromosomes in the GnomAD database, including 50,939 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.30 (7988 hom., cov: 30)
  • Exomes 𝑓: 0.35 (42951 hom.)
• Consequence: FLT3 NM_004119.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.00
• Publications: 5 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP6: Variant 13-28015372-C-T is Benign according to our data. Variant chr13-28015372-C-T is described in ClinVar as Benign. ClinVar VariationId is 1277163.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.408 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.2654-116G>A		intron	N/A	NP_004110.2	P36888-1
	FLT3	NR_130706.2		n.2852-116G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FLT3	ENST00000241453.12	TSL:1 MANE Select	c.2654-116G>A		intron	N/A	ENSP00000241453.7	P36888-1
	FLT3	ENST00000380987.2	TSL:1	n.*566-116G>A		intron	N/A	ENSP00000370374.2	E7ER61
	FLT3	ENST00000864668.1		c.1829-116G>A		intron	N/A	ENSP00000534727.1

Frequencies

GnomAD3 genomes AF: 0.303 AC: 46027 AN: 151682 Hom.: 7984 Cov.: 30

Gnomad AFR AF: 0.152

Gnomad AMI AF: 0.400

Gnomad AMR AF: 0.282

Gnomad ASJ AF: 0.415

Gnomad EAS AF: 0.151

Gnomad SAS AF: 0.215

Gnomad FIN AF: 0.289

Gnomad MID AF: 0.377

Gnomad NFE AF: 0.412

Gnomad OTH AF: 0.350

GnomAD4 exome AF: 0.352 AC: 226371 AN: 643052 Hom.: 42951 AF XY: 0.348 AC XY: 119393 AN XY: 342790

African (AFR) AF: 0.151 AC: 2446 AN: 16250

American (AMR) AF: 0.245 AC: 6988 AN: 28578

Ashkenazi Jewish (ASJ) AF: 0.419 AC: 8442 AN: 20134

East Asian (EAS) AF: 0.152 AC: 4953 AN: 32518

South Asian (SAS) AF: 0.231 AC: 14559 AN: 62906

European-Finnish (FIN) AF: 0.301 AC: 14321 AN: 47508

Middle Eastern (MID) AF: 0.375 AC: 1535 AN: 4096

European-Non Finnish (NFE) AF: 0.406 AC: 161427 AN: 397816

Other (OTH) AF: 0.352 AC: 11700 AN: 33246

GnomAD4 genome AF: 0.303 AC: 46028 AN: 151802 Hom.: 7988 Cov.: 30 AF XY: 0.295 AC XY: 21866 AN XY: 74186

African (AFR) AF: 0.152 AC: 6279 AN: 41406

American (AMR) AF: 0.282 AC: 4295 AN: 15230

Ashkenazi Jewish (ASJ) AF: 0.415 AC: 1439 AN: 3470

East Asian (EAS) AF: 0.151 AC: 778 AN: 5156

South Asian (SAS) AF: 0.216 AC: 1037 AN: 4798

European-Finnish (FIN) AF: 0.289 AC: 3043 AN: 10514

Middle Eastern (MID) AF: 0.371 AC: 109 AN: 294

European-Non Finnish (NFE) AF: 0.412 AC: 27953 AN: 67922

Other (OTH) AF: 0.348 AC: 730 AN: 2100

Alfa AF: 0.372 Hom.: 15725

Bravo AF: 0.295

Asia WGS AF: 0.187 AC: 652 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.63
DANN	Benign	0.78
PhyloP100		-1.0
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: rs9579143; hg19: chr13-28589509;