rs7987649

chr13-28320278-A-Gchr13-28320278-A-T

Variant summary

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

The NM_002019.4(FLT1):c.3175-744T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.349 in 151,978 control chromosomes in the GnomAD database, including 9,347 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 0.35 (9347 hom., cov: 31)
• Consequence: FLT1 NM_002019.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.05

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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.396 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FLT1	NM_002019.4	c.3175-744T>C		intron_variant		ENST00000282397.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FLT1	ENST00000282397.9	c.3175-744T>C		intron_variant		1	NM_002019.4	P1

Frequencies

GnomAD3 genomes AF: 0.349 AC: 53006 AN: 151860 Hom.: 9337 Cov.: 31

Gnomad AFR AF: 0.386

Gnomad AMI AF: 0.342

Gnomad AMR AF: 0.337

Gnomad ASJ AF: 0.278

Gnomad EAS AF: 0.410

Gnomad SAS AF: 0.228

Gnomad FIN AF: 0.337

Gnomad MID AF: 0.313

Gnomad NFE AF: 0.339

Gnomad OTH AF: 0.339

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

GnomAD4 genome AF: 0.349 AC: 53037 AN: 151978 Hom.: 9347 Cov.: 31 AF XY: 0.348 AC XY: 25894 AN XY: 74306

Gnomad4 AFR AF: 0.386

Gnomad4 AMR AF: 0.336

Gnomad4 ASJ AF: 0.278

Gnomad4 EAS AF: 0.410

Gnomad4 SAS AF: 0.226

Gnomad4 FIN AF: 0.337

Gnomad4 NFE AF: 0.339

Gnomad4 OTH AF: 0.336

Alfa AF: 0.337 Hom.: 8466

Bravo AF: 0.356

Asia WGS AF: 0.292 AC: 1022 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	0.088
Dann	Benign	0.66

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs7987649; hg19: chr13-28894415;