NM_002019.4:c.1437-4369G>A

Variant names:

• chr13-28410263-C-T
• rs9508026
• NM_002019.4:c.1437-4369G>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.1437-4369G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.275 in 152,106 control chromosomes in the GnomAD database, including 6,228 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 0.28 (6228 hom., cov: 32)
• Consequence: FLT1 NM_002019.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.103
• Publications: 12 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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.469 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FLT1	NM_002019.4	c.1437-4369G>A		intron_variant	Intron 10 of 29	ENST00000282397.9	NP_002010.2
FLT1	NM_001160030.2	c.1437-4369G>A		intron_variant	Intron 10 of 14		NP_001153502.1
FLT1	NM_001159920.2	c.1437-4369G>A		intron_variant	Intron 10 of 12		NP_001153392.1
FLT1	NM_001160031.1	c.1437-4369G>A		intron_variant	Intron 10 of 11		NP_001153503.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FLT1	ENST00000282397.9	c.1437-4369G>A		intron_variant	Intron 10 of 29	1	NM_002019.4	ENSP00000282397.4

Frequencies

GnomAD3 genomes AF: 0.275 AC: 41863 AN: 151986 Hom.: 6227 Cov.: 32

Gnomad AFR AF: 0.195

Gnomad AMI AF: 0.289

Gnomad AMR AF: 0.215

Gnomad ASJ AF: 0.295

Gnomad EAS AF: 0.486

Gnomad SAS AF: 0.302

Gnomad FIN AF: 0.397

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.300

Gnomad OTH AF: 0.267

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

GnomAD4 genome AF: 0.275 AC: 41876 AN: 152106 Hom.: 6228 Cov.: 32 AF XY: 0.278 AC XY: 20660 AN XY: 74372

African (AFR) AF: 0.195 AC: 8082 AN: 41488

American (AMR) AF: 0.215 AC: 3290 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.295 AC: 1022 AN: 3468

East Asian (EAS) AF: 0.485 AC: 2509 AN: 5176

South Asian (SAS) AF: 0.302 AC: 1455 AN: 4812

European-Finnish (FIN) AF: 0.397 AC: 4194 AN: 10566

Middle Eastern (MID) AF: 0.228 AC: 67 AN: 294

European-Non Finnish (NFE) AF: 0.300 AC: 20421 AN: 67986

Other (OTH) AF: 0.271 AC: 573 AN: 2112

Alfa AF: 0.169 Hom.: 360

Bravo AF: 0.259

Asia WGS AF: 0.367 AC: 1276 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	7.9
DANN	Benign	0.56
PhyloP100		0.10
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: rs9508026; hg19: chr13-28984400; COSMIC: COSV56740655;