rs600640

chr13-28489832-G-Achr13-28489832-G-T

Variant summary

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

The NM_002019.4(FLT1):c.64+4948C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.608 in 151,968 control chromosomes in the GnomAD database, including 28,402 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 0.61 (28402 hom., cov: 32)
• Consequence: FLT1 NM_002019.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.26

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.658 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FLT1	NM_002019.4	c.64+4948C>T		intron_variant		ENST00000282397.9
FLT1	NM_001159920.2	c.64+4948C>T		intron_variant
FLT1	NM_001160030.2	c.64+4948C>T		intron_variant
FLT1	NM_001160031.1	c.64+4948C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FLT1	ENST00000282397.9	c.64+4948C>T		intron_variant		1	NM_002019.4	P1

Frequencies

GnomAD3 genomes AF: 0.608 AC: 92387 AN: 151850 Hom.: 28376 Cov.: 32

Gnomad AFR AF: 0.545

Gnomad AMI AF: 0.689

Gnomad AMR AF: 0.668

Gnomad ASJ AF: 0.680

Gnomad EAS AF: 0.609

Gnomad SAS AF: 0.655

Gnomad FIN AF: 0.503

Gnomad MID AF: 0.639

Gnomad NFE AF: 0.640

Gnomad OTH AF: 0.648

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

GnomAD4 genome AF: 0.608 AC: 92450 AN: 151968 Hom.: 28402 Cov.: 32 AF XY: 0.606 AC XY: 44990 AN XY: 74278

Gnomad4 AFR AF: 0.545

Gnomad4 AMR AF: 0.668

Gnomad4 ASJ AF: 0.680

Gnomad4 EAS AF: 0.609

Gnomad4 SAS AF: 0.653

Gnomad4 FIN AF: 0.503

Gnomad4 NFE AF: 0.640

Gnomad4 OTH AF: 0.646

Alfa AF: 0.636 Hom.: 61026

Bravo AF: 0.616

Asia WGS AF: 0.642 AC: 2234 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.091
Dann	Benign	0.74

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: rs600640; hg19: chr13-29063969;