rs9508025

Variant names:

• chr13-28409926-C-G
• rs9508025
• NM_002019.4:c.1437-4032G>C

Your query was ambiguous. Multiple possible variants found:

• chr13-28409926-C-G
• chr13-28409926-C-T

Variant summary

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

The NM_002019.4(FLT1):​c.1437-4032G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.299 in 151,382 control chromosomes in the GnomAD database, including 7,098 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 0.30 (7098 hom., cov: 30)
• Consequence: FLT1 NM_002019.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.150
• Publications: 20 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=-0.64).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.467 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FLT1	NM_002019.4	c.1437-4032G>C		intron_variant	Intron 10 of 29	ENST00000282397.9	NP_002010.2
FLT1	NM_001160030.2	c.1437-4032G>C		intron_variant	Intron 10 of 14		NP_001153502.1
FLT1	NM_001159920.2	c.1437-4032G>C		intron_variant	Intron 10 of 12		NP_001153392.1
FLT1	NM_001160031.1	c.1437-4032G>C		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.1437-4032G>C		intron_variant	Intron 10 of 29	1	NM_002019.4	ENSP00000282397.4

Frequencies

GnomAD3 genomes AF: 0.299 AC: 45293 AN: 151264 Hom.: 7094 Cov.: 30

Gnomad AFR AF: 0.279

Gnomad AMI AF: 0.291

Gnomad AMR AF: 0.224

Gnomad ASJ AF: 0.294

Gnomad EAS AF: 0.484

Gnomad SAS AF: 0.302

Gnomad FIN AF: 0.399

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.301

Gnomad OTH AF: 0.285

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

GnomAD4 genome AF: 0.299 AC: 45314 AN: 151382 Hom.: 7098 Cov.: 30 AF XY: 0.301 AC XY: 22256 AN XY: 73928

African (AFR) AF: 0.278 AC: 11462 AN: 41200

American (AMR) AF: 0.223 AC: 3403 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.294 AC: 1020 AN: 3464

East Asian (EAS) AF: 0.483 AC: 2480 AN: 5136

South Asian (SAS) AF: 0.303 AC: 1446 AN: 4776

European-Finnish (FIN) AF: 0.399 AC: 4148 AN: 10386

Middle Eastern (MID) AF: 0.241 AC: 71 AN: 294

European-Non Finnish (NFE) AF: 0.301 AC: 20412 AN: 67874

Other (OTH) AF: 0.289 AC: 608 AN: 2104

Alfa AF: 0.292 Hom.: 786

Bravo AF: 0.286

Asia WGS AF: 0.372 AC: 1293 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	11
DANN	Benign	0.82
PhyloP100		0.15
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: rs9508025; hg19: chr13-28984063; COSMIC: COSV56740646;