rs678714

Positions:

• chr13-28491920-T-A
• chr13-28491920-T-C

Variant summary

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

The NM_002019.4(FLT1):​c.64+2860A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.899 in 152,258 control chromosomes in the GnomAD database, including 61,866 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 0.90 (61866 hom., cov: 33)
• Consequence: FLT1 NM_002019.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.695

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=-0.79).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.964 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FLT1	NM_002019.4	c.64+2860A>T		intron_variant		ENST00000282397.9	NP_002010.2
FLT1	NM_001159920.2	c.64+2860A>T		intron_variant			NP_001153392.1
FLT1	NM_001160030.2	c.64+2860A>T		intron_variant			NP_001153502.1
FLT1	NM_001160031.1	c.64+2860A>T		intron_variant			NP_001153503.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FLT1	ENST00000282397.9	c.64+2860A>T		intron_variant		1	NM_002019.4	ENSP00000282397	P1

Frequencies

GnomAD3 genomes AF: 0.899 AC: 136749 AN: 152140 Hom.: 61814 Cov.: 33

Gnomad AFR AF: 0.972

Gnomad AMI AF: 0.901

Gnomad AMR AF: 0.910

Gnomad ASJ AF: 0.944

Gnomad EAS AF: 0.707

Gnomad SAS AF: 0.833

Gnomad FIN AF: 0.762

Gnomad MID AF: 0.902

Gnomad NFE AF: 0.890

Gnomad OTH AF: 0.906

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

GnomAD4 genome AF: 0.899 AC: 136861 AN: 152258 Hom.: 61866 Cov.: 33 AF XY: 0.891 AC XY: 66296 AN XY: 74438

Gnomad4 AFR AF: 0.972

Gnomad4 AMR AF: 0.910

Gnomad4 ASJ AF: 0.944

Gnomad4 EAS AF: 0.708

Gnomad4 SAS AF: 0.831

Gnomad4 FIN AF: 0.762

Gnomad4 NFE AF: 0.890

Gnomad4 OTH AF: 0.903

Alfa AF: 0.898 Hom.: 7478

Bravo AF: 0.915

Asia WGS AF: 0.812 AC: 2826 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	3.2
DANN	Benign	0.68

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: rs678714; hg19: chr13-29066057;