13-28318848-C-T

Variant names:

• chr13-28318848-C-T
• rs9319425
• NM_002019.4:c.3286+575G>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.3286+575G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.544 in 151,998 control chromosomes in the GnomAD database, including 22,507 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 0.54 (22507 hom., cov: 32)
• Consequence: FLT1 NM_002019.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.23
• Publications: 12 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]

LOC124903141 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.561 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002019.4. 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
	FLT1	NM_002019.4	MANE Select	c.3286+575G>A		intron	N/A	NP_002010.2	P17948-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FLT1	ENST00000282397.9	TSL:1 MANE Select	c.3286+575G>A		intron	N/A	ENSP00000282397.4	P17948-1
	FLT1	ENST00000540678.2	TSL:1	n.1173+575G>A		intron	N/A
	FLT1	ENST00000543394.2	TSL:1	n.511+575G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.544 AC: 82590 AN: 151880 Hom.: 22479 Cov.: 32

Gnomad AFR AF: 0.551

Gnomad AMI AF: 0.629

Gnomad AMR AF: 0.570

Gnomad ASJ AF: 0.533

Gnomad EAS AF: 0.522

Gnomad SAS AF: 0.556

Gnomad FIN AF: 0.519

Gnomad MID AF: 0.592

Gnomad NFE AF: 0.536

Gnomad OTH AF: 0.574

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

GnomAD4 genome AF: 0.544 AC: 82668 AN: 151998 Hom.: 22507 Cov.: 32 AF XY: 0.545 AC XY: 40486 AN XY: 74308

African (AFR) AF: 0.551 AC: 22826 AN: 41422

American (AMR) AF: 0.571 AC: 8718 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.533 AC: 1847 AN: 3466

East Asian (EAS) AF: 0.522 AC: 2696 AN: 5160

South Asian (SAS) AF: 0.554 AC: 2672 AN: 4820

European-Finnish (FIN) AF: 0.519 AC: 5486 AN: 10580

Middle Eastern (MID) AF: 0.592 AC: 174 AN: 294

European-Non Finnish (NFE) AF: 0.536 AC: 36457 AN: 67960

Other (OTH) AF: 0.578 AC: 1218 AN: 2108

Alfa AF: 0.539 Hom.: 20127

Bravo AF: 0.551

Asia WGS AF: 0.572 AC: 1988 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.0040
DANN	Benign	0.50
PhyloP100		-4.2
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: rs9319425; hg19: chr13-28892985;