chr13-28399484-G-A

Position:

• chr13-28399484-G-A

Variant summary

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

The NM_002019.4(FLT1):​c.1552-2416C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.303 in 151,960 control chromosomes in the GnomAD database, including 7,227 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 0.30 (7227 hom., cov: 32)
• Consequence: FLT1 NM_002019.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.04

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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.427 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FLT1	NM_002019.4	c.1552-2416C>T		intron_variant		ENST00000282397.9	NP_002010.2
FLT1	NM_001159920.2	c.1552-2416C>T		intron_variant			NP_001153392.1
FLT1	NM_001160030.2	c.1552-2416C>T		intron_variant			NP_001153502.1
FLT1	NM_001160031.1	c.1552-366C>T		intron_variant			NP_001153503.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FLT1	ENST00000282397.9	c.1552-2416C>T		intron_variant		1	NM_002019.4	ENSP00000282397	P1

Frequencies

GnomAD3 genomes AF: 0.303 AC: 45967 AN: 151842 Hom.: 7222 Cov.: 32

Gnomad AFR AF: 0.295

Gnomad AMI AF: 0.292

Gnomad AMR AF: 0.225

Gnomad ASJ AF: 0.291

Gnomad EAS AF: 0.443

Gnomad SAS AF: 0.314

Gnomad FIN AF: 0.397

Gnomad MID AF: 0.223

Gnomad NFE AF: 0.300

Gnomad OTH AF: 0.287

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

GnomAD4 genome AF: 0.303 AC: 45993 AN: 151960 Hom.: 7227 Cov.: 32 AF XY: 0.304 AC XY: 22590 AN XY: 74266

Gnomad4 AFR AF: 0.295

Gnomad4 AMR AF: 0.224

Gnomad4 ASJ AF: 0.291

Gnomad4 EAS AF: 0.442

Gnomad4 SAS AF: 0.314

Gnomad4 FIN AF: 0.397

Gnomad4 NFE AF: 0.300

Gnomad4 OTH AF: 0.291

Alfa AF: 0.303 Hom.: 10807

Bravo AF: 0.289

Asia WGS AF: 0.372 AC: 1294 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	12
DANN	Benign	0.81

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: rs9319428; hg19: chr13-28973621; COSMIC: COSV56740619;