rs3751395

chr13-28384818-C-Achr13-28384818-C-G

Variant summary

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

The NM_002019.4(FLT1):c.2116+67G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.487 in 1,453,928 control chromosomes in the GnomAD database, including 178,122 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 0.53 (21820 hom., cov: 32)
  • Exomes 𝑓: 0.48 (156302 hom.)
• Consequence: FLT1 NM_002019.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.314

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.629 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FLT1	NM_002019.4	c.2116+67G>T		intron_variant		ENST00000282397.9
FLT1	NM_001160030.2	c.2116+67G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FLT1	ENST00000282397.9	c.2116+67G>T		intron_variant		1	NM_002019.4	P1
FLT1	ENST00000541932.5	c.2116+67G>T		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.527 AC: 79964 AN: 151736 Hom.: 21785 Cov.: 32

Gnomad AFR AF: 0.636

Gnomad AMI AF: 0.502

Gnomad AMR AF: 0.630

Gnomad ASJ AF: 0.424

Gnomad EAS AF: 0.627

Gnomad SAS AF: 0.612

Gnomad FIN AF: 0.369

Gnomad MID AF: 0.509

Gnomad NFE AF: 0.454

Gnomad OTH AF: 0.546

GnomAD4 exome AF: 0.482 AC: 627958 AN: 1302074 Hom.: 156302 AF XY: 0.484 AC XY: 317958 AN XY: 656460

Gnomad4 AFR exome AF: 0.636

Gnomad4 AMR exome AF: 0.722

Gnomad4 ASJ exome AF: 0.417

Gnomad4 EAS exome AF: 0.666

Gnomad4 SAS exome AF: 0.604

Gnomad4 FIN exome AF: 0.377

Gnomad4 NFE exome AF: 0.455

Gnomad4 OTH exome AF: 0.495

GnomAD4 genome AF: 0.527 AC: 80051 AN: 151854 Hom.: 21820 Cov.: 32 AF XY: 0.529 AC XY: 39268 AN XY: 74188

Gnomad4 AFR AF: 0.636

Gnomad4 AMR AF: 0.631

Gnomad4 ASJ AF: 0.424

Gnomad4 EAS AF: 0.628

Gnomad4 SAS AF: 0.612

Gnomad4 FIN AF: 0.369

Gnomad4 NFE AF: 0.454

Gnomad4 OTH AF: 0.543

Alfa AF: 0.478 Hom.: 18087

Bravo AF: 0.554

Asia WGS AF: 0.613 AC: 2137 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	2.0
Dann	Benign	0.33

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: rs3751395; hg19: chr13-28958955; COSMIC: COSV56719104; COSMIC: COSV56719104;