rs4497507

Variant names:

• chr13-28015525-C-G
• rs4497507
• NM_004119.3:c.2653+65G>C

Your query was ambiguous. Multiple possible variants found:

• chr13-28015525-C-G
• chr13-28015525-C-T

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.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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -4.17
• Publications: 3 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=-0.91).
• BP6: Variant 13-28015525-C-G is Benign according to our data. Variant chr13-28015525-C-G is described in ClinVar as Benign. ClinVar VariationId is 1256865.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.991 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.2653+65G>C		intron	N/A	NP_004110.2	P36888-1
	FLT3	NR_130706.2		n.2851+65G>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FLT3	ENST00000241453.12	TSL:1 MANE Select	c.2653+65G>C		intron	N/A	ENSP00000241453.7	P36888-1
	FLT3	ENST00000380987.2	TSL:1	n.*565+65G>C		intron	N/A	ENSP00000370374.2	E7ER61
	FLT3	ENST00000864668.1		c.1828+65G>C		intron	N/A	ENSP00000534727.1

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

African (AFR) AF: 0.510 AC: 8704 AN: 17082

American (AMR) AF: 0.968 AC: 31461 AN: 32502

Ashkenazi Jewish (ASJ) AF: 0.997 AC: 18377 AN: 18438

East Asian (EAS) AF: 1.00 AC: 35154 AN: 35166

South Asian (SAS) AF: 0.998 AC: 64180 AN: 64334

European-Finnish (FIN) AF: 0.999 AC: 46346 AN: 46374

Middle Eastern (MID) AF: 0.962 AC: 2644 AN: 2748

European-Non Finnish (NFE) AF: 0.997 AC: 379803 AN: 380784

Other (OTH) AF: 0.961 AC: 30993 AN: 32252

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

African (AFR) AF: 0.517 AC: 19720 AN: 38130

American (AMR) AF: 0.924 AC: 12569 AN: 13600

Ashkenazi Jewish (ASJ) AF: 0.997 AC: 3377 AN: 3386

East Asian (EAS) AF: 1.00 AC: 4502 AN: 4502

South Asian (SAS) AF: 0.995 AC: 3800 AN: 3820

European-Finnish (FIN) AF: 0.999 AC: 8259 AN: 8266

Middle Eastern (MID) AF: 0.887 AC: 252 AN: 284

European-Non Finnish (NFE) AF: 0.997 AC: 65233 AN: 65426

Other (OTH) AF: 0.894 AC: 1711 AN: 1914

Alfa AF: 0.871 Hom.: 2259

Bravo AF: 0.841

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	-0.91
CADD	Benign	1.3
DANN	Benign	0.29
PhyloP100		-4.2
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4497507; hg19: chr13-28589662;