13-28318848-C-T

Variant names:

• chr13-28318848-C-T
• rs9319425
• NM_002019.4:c.3286+575G>A

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FLT1	NM_002019.4	c.3286+575G>A		intron_variant	Intron 24 of 29	ENST00000282397.9	NP_002010.2
LOC124903141	XR_007063736.1	n.581C>T		non_coding_transcript_exon_variant	Exon 3 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FLT1	ENST00000282397.9	c.3286+575G>A		intron_variant	Intron 24 of 29	1	NM_002019.4	ENSP00000282397.4

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

Gnomad4 AFR AF: 0.551

Gnomad4 AMR AF: 0.571

Gnomad4 ASJ AF: 0.533

Gnomad4 EAS AF: 0.522

Gnomad4 SAS AF: 0.554

Gnomad4 FIN AF: 0.519

Gnomad4 NFE AF: 0.536

Gnomad4 OTH AF: 0.578

Alfa AF: 0.539 Hom.: 12177

Bravo AF: 0.551

Asia WGS AF: 0.572 AC: 1988 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.0040
DANN	Benign	0.50

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

Publications

LitVar

Other links and lift over

dbSNP: rs9319425; hg19: chr13-28892985;