rs2296283

chr13-28389565-G-Achr13-28389565-G-Cchr13-28389565-G-T

Variant summary

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

The ENST00000615840.5(FLT1):c.*136C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.517 in 1,435,328 control chromosomes in the GnomAD database, including 197,498 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 0.42 (15610 hom., cov: 32)
  • Exomes 𝑓: 0.53 (181888 hom.)
• Consequence: FLT1 ENST00000615840.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.823

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=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.532 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FLT1	NM_002019.4	c.1969+231C>T		intron_variant		ENST00000282397.9
FLT1	NM_001159920.2	c.*136C>T		3_prime_UTR_variant	13/13
FLT1	NM_001160030.2	c.1969+231C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FLT1	ENST00000615840.5	c.*136C>T		3_prime_UTR_variant	13/13	1
FLT1	ENST00000282397.9	c.1969+231C>T		intron_variant		1	NM_002019.4	P1
FLT1	ENST00000541932.5	c.1969+231C>T		intron_variant		1
FLT1	ENST00000639477.1	c.*39C>T		3_prime_UTR_variant	14/14	5

Frequencies

GnomAD3 genomes AF: 0.424 AC: 64502 AN: 152008 Hom.: 15614 Cov.: 32

Gnomad AFR AF: 0.177

Gnomad AMI AF: 0.603

Gnomad AMR AF: 0.452

Gnomad ASJ AF: 0.597

Gnomad EAS AF: 0.527

Gnomad SAS AF: 0.496

Gnomad FIN AF: 0.466

Gnomad MID AF: 0.592

Gnomad NFE AF: 0.536

Gnomad OTH AF: 0.462

GnomAD4 exome AF: 0.528 AC: 678128 AN: 1283202 Hom.: 181888 Cov.: 49 AF XY: 0.530 AC XY: 329222 AN XY: 621488

Gnomad4 AFR exome AF: 0.166

Gnomad4 AMR exome AF: 0.454

Gnomad4 ASJ exome AF: 0.578

Gnomad4 EAS exome AF: 0.556

Gnomad4 SAS exome AF: 0.502

Gnomad4 FIN exome AF: 0.459

Gnomad4 NFE exome AF: 0.543

Gnomad4 OTH exome AF: 0.509

GnomAD4 genome AF: 0.424 AC: 64512 AN: 152126 Hom.: 15610 Cov.: 32 AF XY: 0.423 AC XY: 31469 AN XY: 74390

Gnomad4 AFR AF: 0.176

Gnomad4 AMR AF: 0.453

Gnomad4 ASJ AF: 0.597

Gnomad4 EAS AF: 0.528

Gnomad4 SAS AF: 0.495

Gnomad4 FIN AF: 0.466

Gnomad4 NFE AF: 0.536

Gnomad4 OTH AF: 0.459

Alfa AF: 0.436 Hom.: 2270

Bravo AF: 0.415

Asia WGS AF: 0.504 AC: 1751 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	15
Dann	Benign	0.79

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: rs2296283; hg19: chr13-28963702;