rs2491222

Variant names:

• chr13-28033779-T-A
• rs2491222
• NM_004119.3:c.1942+108A>T

Your query was ambiguous. Multiple possible variants found:

• chr13-28033779-T-A
• chr13-28033779-T-C
• chr13-28033779-T-G

Variant summary

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

The ENST00000241453.12(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 ENST00000241453.12 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.52
• Publications: 7 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=-0.87).
• BP6: Variant 13-28033779-T-A is Benign according to our data. Variant chr13-28033779-T-A is described in ClinVar as Benign. ClinVar VariationId is 1232565.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.767 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000241453.12. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FLT3	NM_004119.3	MANE Select	c.1942+108A>T		intron	N/A	NP_004110.2
	FLT3	NR_130706.2		n.2008+108A>T		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FLT3	ENST00000241453.12	TSL:1 MANE Select	c.1942+108A>T		intron	N/A	ENSP00000241453.7
	FLT3	ENST00000380987.2	TSL:1	n.1942+108A>T		intron	N/A	ENSP00000370374.2

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

African (AFR) AF: 0.302 AC: 5577 AN: 18470

American (AMR) AF: 0.707 AC: 24016 AN: 33958

Ashkenazi Jewish (ASJ) AF: 0.717 AC: 13123 AN: 18294

East Asian (EAS) AF: 0.684 AC: 24510 AN: 35820

South Asian (SAS) AF: 0.595 AC: 35584 AN: 59778

European-Finnish (FIN) AF: 0.806 AC: 37775 AN: 46852

Middle Eastern (MID) AF: 0.655 AC: 2677 AN: 4090

European-Non Finnish (NFE) AF: 0.777 AC: 357402 AN: 460262

Other (OTH) AF: 0.726 AC: 25549 AN: 35212

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

African (AFR) AF: 0.309 AC: 12815 AN: 41510

American (AMR) AF: 0.665 AC: 10159 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.724 AC: 2512 AN: 3470

East Asian (EAS) AF: 0.726 AC: 3763 AN: 5180

South Asian (SAS) AF: 0.591 AC: 2848 AN: 4818

European-Finnish (FIN) AF: 0.797 AC: 8432 AN: 10582

Middle Eastern (MID) AF: 0.633 AC: 186 AN: 294

European-Non Finnish (NFE) AF: 0.773 AC: 52537 AN: 67990

Other (OTH) AF: 0.654 AC: 1383 AN: 2114

Alfa AF: 0.678 Hom.: 4610

Bravo AF: 0.608

Asia WGS AF: 0.639 AC: 2225 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	-0.87
CADD	Benign	0.71
DANN	Benign	0.35
PhyloP100		-1.5
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: rs2491222; hg19: chr13-28607916;