rs3751397

Positions:

• chr13-28386456-T-A
• chr13-28386456-T-C
• chr13-28386456-T-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001159920.2(FLT1):​c.*3245A>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 0.513 in 1,041,944 control chromosomes in the GnomAD database, including 140,888 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 0.43 (15684 hom., cov: 32)
  • Exomes 𝑓: 0.53 (125204 hom.)
• Consequence: FLT1 NM_001159920.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0750

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.37).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.524 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FLT1	NM_002019.4	c.1970-1425A>T		intron_variant		ENST00000282397.9	NP_002010.2
FLT1	NM_001159920.2	c.*3245A>T		3_prime_UTR_variant	13/13		NP_001153392.1
FLT1	NM_001160030.2	c.1970-1425A>T		intron_variant			NP_001153502.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FLT1	ENST00000615840	c.*3245A>T		3_prime_UTR_variant	13/13	1		ENSP00000484039.1
FLT1	ENST00000282397.9	c.1970-1425A>T		intron_variant		1	NM_002019.4	ENSP00000282397.4
FLT1	ENST00000541932.5	c.1970-1425A>T		intron_variant		1		ENSP00000437631.1
FLT1	ENST00000639477	c.*3148A>T		3_prime_UTR_variant	14/14	5		ENSP00000491097.1

Frequencies

GnomAD3 genomes AF: 0.433 AC: 65715 AN: 151916 Hom.: 15678 Cov.: 32

Gnomad AFR AF: 0.215

Gnomad AMI AF: 0.610

Gnomad AMR AF: 0.481

Gnomad ASJ AF: 0.565

Gnomad EAS AF: 0.535

Gnomad SAS AF: 0.480

Gnomad FIN AF: 0.451

Gnomad MID AF: 0.563

Gnomad NFE AF: 0.529

Gnomad OTH AF: 0.478

GnomAD4 exome AF: 0.527 AC: 469019 AN: 889910 Hom.: 125204 Cov.: 25 AF XY: 0.529 AC XY: 217572 AN XY: 411246

Gnomad4 AFR exome AF: 0.198

Gnomad4 AMR exome AF: 0.496

Gnomad4 ASJ exome AF: 0.535

Gnomad4 EAS exome AF: 0.561

Gnomad4 SAS exome AF: 0.485

Gnomad4 FIN exome AF: 0.447

Gnomad4 NFE exome AF: 0.536

Gnomad4 OTH exome AF: 0.503

GnomAD4 genome AF: 0.432 AC: 65739 AN: 152034 Hom.: 15684 Cov.: 32 AF XY: 0.432 AC XY: 32091 AN XY: 74318

Gnomad4 AFR AF: 0.215

Gnomad4 AMR AF: 0.482

Gnomad4 ASJ AF: 0.565

Gnomad4 EAS AF: 0.536

Gnomad4 SAS AF: 0.480

Gnomad4 FIN AF: 0.451

Gnomad4 NFE AF: 0.529

Gnomad4 OTH AF: 0.476

Alfa AF: 0.470 Hom.: 2171

Bravo AF: 0.427

Asia WGS AF: 0.493 AC: 1715 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
CADD	Benign	15
DANN	Benign	0.84

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: rs3751397; hg19: chr13-28960593;