13-28427584-C-T

Variant names:

• chr13-28427584-C-T
• rs2281827
• NM_002019.4:c.1276+168G>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.1276+168G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.198 in 152,108 control chromosomes in the GnomAD database, including 3,417 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 0.20 (3417 hom., cov: 32)
• Consequence: FLT1 NM_002019.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.679
• Publications: 9 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=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.386 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FLT1	NM_002019.4	c.1276+168G>A		intron_variant	Intron 9 of 29	ENST00000282397.9	NP_002010.2
FLT1	NM_001160030.2	c.1276+168G>A		intron_variant	Intron 9 of 14		NP_001153502.1
FLT1	NM_001159920.2	c.1276+168G>A		intron_variant	Intron 9 of 12		NP_001153392.1
FLT1	NM_001160031.1	c.1276+168G>A		intron_variant	Intron 9 of 11		NP_001153503.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FLT1	ENST00000282397.9	c.1276+168G>A		intron_variant	Intron 9 of 29	1	NM_002019.4	ENSP00000282397.4

Frequencies

GnomAD3 genomes AF: 0.198 AC: 30027 AN: 151990 Hom.: 3415 Cov.: 32

Gnomad AFR AF: 0.0865

Gnomad AMI AF: 0.155

Gnomad AMR AF: 0.229

Gnomad ASJ AF: 0.293

Gnomad EAS AF: 0.289

Gnomad SAS AF: 0.401

Gnomad FIN AF: 0.201

Gnomad MID AF: 0.335

Gnomad NFE AF: 0.230

Gnomad OTH AF: 0.237

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

GnomAD4 genome AF: 0.198 AC: 30044 AN: 152108 Hom.: 3417 Cov.: 32 AF XY: 0.203 AC XY: 15080 AN XY: 74346

African (AFR) AF: 0.0865 AC: 3587 AN: 41474

American (AMR) AF: 0.229 AC: 3504 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.293 AC: 1016 AN: 3468

East Asian (EAS) AF: 0.290 AC: 1504 AN: 5178

South Asian (SAS) AF: 0.400 AC: 1931 AN: 4822

European-Finnish (FIN) AF: 0.201 AC: 2125 AN: 10572

Middle Eastern (MID) AF: 0.333 AC: 98 AN: 294

European-Non Finnish (NFE) AF: 0.230 AC: 15636 AN: 67990

Other (OTH) AF: 0.237 AC: 502 AN: 2114

Alfa AF: 0.199 Hom.: 1673

Bravo AF: 0.192

Asia WGS AF: 0.374 AC: 1299 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.45
DANN	Benign	0.79
PhyloP100		-0.68
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: rs2281827; hg19: chr13-29001721;