rs638889

chr13-28470215-T-Cchr13-28470215-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002019.4(FLT1):c.65-2598A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.238 in 152,104 control chromosomes in the GnomAD database, including 5,827 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 0.24 (5827 hom., cov: 32)
• Consequence: FLT1 NM_002019.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.31

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.434 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FLT1	NM_002019.4	c.65-2598A>G		intron_variant		ENST00000282397.9
FLT1	NM_001159920.2	c.65-2598A>G		intron_variant
FLT1	NM_001160030.2	c.65-2598A>G		intron_variant
FLT1	NM_001160031.1	c.65-2598A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FLT1	ENST00000282397.9	c.65-2598A>G		intron_variant		1	NM_002019.4	P1

Frequencies

GnomAD3 genomes AF: 0.237 AC: 36071 AN: 151984 Hom.: 5799 Cov.: 32

Gnomad AFR AF: 0.439

Gnomad AMI AF: 0.101

Gnomad AMR AF: 0.273

Gnomad ASJ AF: 0.115

Gnomad EAS AF: 0.0467

Gnomad SAS AF: 0.197

Gnomad FIN AF: 0.147

Gnomad MID AF: 0.131

Gnomad NFE AF: 0.148

Gnomad OTH AF: 0.217

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

GnomAD4 genome AF: 0.238 AC: 36150 AN: 152104 Hom.: 5827 Cov.: 32 AF XY: 0.236 AC XY: 17569 AN XY: 74370

Gnomad4 AFR AF: 0.440

Gnomad4 AMR AF: 0.273

Gnomad4 ASJ AF: 0.115

Gnomad4 EAS AF: 0.0466

Gnomad4 SAS AF: 0.197

Gnomad4 FIN AF: 0.147

Gnomad4 NFE AF: 0.147

Gnomad4 OTH AF: 0.216

Alfa AF: 0.115 Hom.: 254

Bravo AF: 0.256

Asia WGS AF: 0.140 AC: 487 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	0.23
Dann	Benign	0.38

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: rs638889; hg19: chr13-29044352;