13-28432710-C-T

Variant names:

• chr13-28432710-C-T
• rs3794405
• NM_002019.4:c.813+1109G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002019.4(FLT1):​c.813+1109G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.768 in 152,198 control chromosomes in the GnomAD database, including 44,990 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 0.77 (44990 hom., cov: 34)
• Consequence: FLT1 NM_002019.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.46
• Publications: 10 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.772 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002019.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FLT1	NM_002019.4	MANE Select	c.813+1109G>A		intron	N/A	NP_002010.2
	FLT1	NM_001160030.2		c.813+1109G>A		intron	N/A	NP_001153502.1
	FLT1	NM_001159920.2		c.813+1109G>A		intron	N/A	NP_001153392.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FLT1	ENST00000282397.9	TSL:1 MANE Select	c.813+1109G>A		intron	N/A	ENSP00000282397.4
	FLT1	ENST00000541932.5	TSL:1	c.813+1109G>A		intron	N/A	ENSP00000437631.1
	FLT1	ENST00000615840.5	TSL:1	c.813+1109G>A		intron	N/A	ENSP00000484039.1

Frequencies

GnomAD3 genomes AF: 0.768 AC: 116752 AN: 152080 Hom.: 44972 Cov.: 34

Gnomad AFR AF: 0.773

Gnomad AMI AF: 0.874

Gnomad AMR AF: 0.746

Gnomad ASJ AF: 0.733

Gnomad EAS AF: 0.711

Gnomad SAS AF: 0.600

Gnomad FIN AF: 0.830

Gnomad MID AF: 0.620

Gnomad NFE AF: 0.778

Gnomad OTH AF: 0.741

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

GnomAD4 genome AF: 0.768 AC: 116820 AN: 152198 Hom.: 44990 Cov.: 34 AF XY: 0.763 AC XY: 56767 AN XY: 74408

African (AFR) AF: 0.773 AC: 32080 AN: 41518

American (AMR) AF: 0.746 AC: 11399 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.733 AC: 2542 AN: 3468

East Asian (EAS) AF: 0.710 AC: 3680 AN: 5184

South Asian (SAS) AF: 0.600 AC: 2897 AN: 4826

European-Finnish (FIN) AF: 0.830 AC: 8789 AN: 10594

Middle Eastern (MID) AF: 0.622 AC: 183 AN: 294

European-Non Finnish (NFE) AF: 0.778 AC: 52886 AN: 68000

Other (OTH) AF: 0.742 AC: 1567 AN: 2112

Alfa AF: 0.768 Hom.: 34432

Bravo AF: 0.766

Asia WGS AF: 0.617 AC: 2146 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.0020
DANN	Benign	0.66
PhyloP100		-4.5
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3794405; hg19: chr13-29006847;