13-28469004-C-T

Variant names:

• chr13-28469004-C-T
• rs718273
• NM_002019.4:c.65-1387G>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.65-1387G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.226 in 152,078 control chromosomes in the GnomAD database, including 4,605 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 0.23 (4605 hom., cov: 32)
• Consequence: FLT1 NM_002019.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.839
• Publications: 7 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=-1.01).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.303 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FLT1	NM_002019.4	c.65-1387G>A		intron_variant	Intron 1 of 29	ENST00000282397.9	NP_002010.2
FLT1	NM_001160030.2	c.65-1387G>A		intron_variant	Intron 1 of 14		NP_001153502.1
FLT1	NM_001159920.2	c.65-1387G>A		intron_variant	Intron 1 of 12		NP_001153392.1
FLT1	NM_001160031.1	c.65-1387G>A		intron_variant	Intron 1 of 11		NP_001153503.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FLT1	ENST00000282397.9	c.65-1387G>A		intron_variant	Intron 1 of 29	1	NM_002019.4	ENSP00000282397.4

Frequencies

GnomAD3 genomes AF: 0.227 AC: 34442 AN: 151960 Hom.: 4602 Cov.: 32

Gnomad AFR AF: 0.0965

Gnomad AMI AF: 0.414

Gnomad AMR AF: 0.227

Gnomad ASJ AF: 0.327

Gnomad EAS AF: 0.182

Gnomad SAS AF: 0.0946

Gnomad FIN AF: 0.250

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.307

Gnomad OTH AF: 0.230

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

GnomAD4 genome AF: 0.226 AC: 34440 AN: 152078 Hom.: 4605 Cov.: 32 AF XY: 0.221 AC XY: 16463 AN XY: 74332

African (AFR) AF: 0.0966 AC: 4010 AN: 41510

American (AMR) AF: 0.227 AC: 3468 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.327 AC: 1134 AN: 3470

East Asian (EAS) AF: 0.182 AC: 937 AN: 5154

South Asian (SAS) AF: 0.0949 AC: 457 AN: 4818

European-Finnish (FIN) AF: 0.250 AC: 2642 AN: 10566

Middle Eastern (MID) AF: 0.276 AC: 81 AN: 294

European-Non Finnish (NFE) AF: 0.307 AC: 20856 AN: 67966

Other (OTH) AF: 0.226 AC: 478 AN: 2112

Alfa AF: 0.260 Hom.: 2871

Bravo AF: 0.222

Asia WGS AF: 0.102 AC: 355 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.1
DANN	Benign	0.62
PhyloP100		-0.84
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: rs718273; hg19: chr13-29043141;