13-28326373-C-T

Variant names:

• chr13-28326373-C-T
• rs17619601
• NM_002019.4:c.2796+1089G>A

Variant summary

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

The NM_002019.4(FLT1):​c.2796+1089G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0502 in 152,208 control chromosomes in the GnomAD database, including 263 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 0.050 (263 hom., cov: 31)
• Consequence: FLT1 NM_002019.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0580
• Publications: 4 publications found

Genes affected

FLT1 (HGNC:3763): (fms related receptor tyrosine kinase 1) This gene encodes a member of the vascular endothelial growth factor receptor (VEGFR) family. VEGFR family members are receptor tyrosine kinases (RTKs) which contain an extracellular ligand-binding region with seven immunoglobulin (Ig)-like domains, a transmembrane segment, and a tyrosine kinase (TK) domain within the cytoplasmic domain. This protein binds to VEGFR-A, VEGFR-B and placental growth factor and plays an important role in angiogenesis and vasculogenesis. Expression of this receptor is found in vascular endothelial cells, placental trophoblast cells and peripheral blood monocytes. Multiple transcript variants encoding different isoforms have been found for this gene. Isoforms include a full-length transmembrane receptor isoform and shortened, soluble isoforms. The soluble isoforms are associated with the onset of pre-eclampsia.[provided by RefSeq, May 2009]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0737 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FLT1	NM_002019.4	c.2796+1089G>A		intron_variant	Intron 20 of 29	ENST00000282397.9	NP_002010.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FLT1	ENST00000282397.9	c.2796+1089G>A		intron_variant	Intron 20 of 29	1	NM_002019.4	ENSP00000282397.4
FLT1	ENST00000540678.2	n.683+1089G>A		intron_variant	Intron 7 of 16	1
FLT1	ENST00000615611.4	n.214+1089G>A		intron_variant	Intron 2 of 11	1
FLT1	ENST00000706527.1	n.621+1089G>A		intron_variant	Intron 6 of 15

Frequencies

GnomAD3 genomes AF: 0.0502 AC: 7640 AN: 152090 Hom.: 262 Cov.: 31

Gnomad AFR AF: 0.0125

Gnomad AMI AF: 0.0746

Gnomad AMR AF: 0.0427

Gnomad ASJ AF: 0.0427

Gnomad EAS AF: 0.00134

Gnomad SAS AF: 0.0798

Gnomad FIN AF: 0.0722

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0733

Gnomad OTH AF: 0.0455

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0502 AC: 7635 AN: 152208 Hom.: 263 Cov.: 31 AF XY: 0.0515 AC XY: 3831 AN XY: 74408

African (AFR) AF: 0.0125 AC: 519 AN: 41556

American (AMR) AF: 0.0424 AC: 648 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0427 AC: 148 AN: 3464

East Asian (EAS) AF: 0.00135 AC: 7 AN: 5194

South Asian (SAS) AF: 0.0803 AC: 387 AN: 4820

European-Finnish (FIN) AF: 0.0722 AC: 764 AN: 10582

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.0733 AC: 4986 AN: 67998

Other (OTH) AF: 0.0451 AC: 95 AN: 2108

Alfa AF: 0.0459 Hom.: 105

Bravo AF: 0.0453

Asia WGS AF: 0.0290 AC: 104 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.1
DANN	Benign	0.57
PhyloP100		0.058
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: rs17619601; hg19: chr13-28900510;