rs9319427

Variant names:

• chr13-28398027-A-G
• rs9319427
• NM_002019.4:c.1552-959T>C

Your query was ambiguous. Multiple possible variants found:

• chr13-28398027-A-G
• chr13-28398027-A-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.1552-959T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.419 in 151,934 control chromosomes in the GnomAD database, including 15,212 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 0.42 (15212 hom., cov: 31)
• Consequence: FLT1 NM_002019.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.90
• 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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.523 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FLT1	NM_002019.4	c.1552-959T>C		intron_variant	Intron 11 of 29	ENST00000282397.9	NP_002010.2
FLT1	NM_001160030.2	c.1552-959T>C		intron_variant	Intron 11 of 14		NP_001153502.1
FLT1	NM_001159920.2	c.1552-959T>C		intron_variant	Intron 11 of 12		NP_001153392.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FLT1	ENST00000282397.9	c.1552-959T>C		intron_variant	Intron 11 of 29	1	NM_002019.4	ENSP00000282397.4

Frequencies

GnomAD3 genomes AF: 0.420 AC: 63690 AN: 151816 Hom.: 15215 Cov.: 31

Gnomad AFR AF: 0.174

Gnomad AMI AF: 0.595

Gnomad AMR AF: 0.449

Gnomad ASJ AF: 0.597

Gnomad EAS AF: 0.533

Gnomad SAS AF: 0.509

Gnomad FIN AF: 0.460

Gnomad MID AF: 0.601

Gnomad NFE AF: 0.528

Gnomad OTH AF: 0.460

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

GnomAD4 genome AF: 0.419 AC: 63698 AN: 151934 Hom.: 15212 Cov.: 31 AF XY: 0.419 AC XY: 31105 AN XY: 74212

African (AFR) AF: 0.174 AC: 7205 AN: 41478

American (AMR) AF: 0.450 AC: 6856 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.597 AC: 2070 AN: 3466

East Asian (EAS) AF: 0.534 AC: 2765 AN: 5178

South Asian (SAS) AF: 0.508 AC: 2434 AN: 4796

European-Finnish (FIN) AF: 0.460 AC: 4841 AN: 10520

Middle Eastern (MID) AF: 0.599 AC: 176 AN: 294

European-Non Finnish (NFE) AF: 0.528 AC: 35849 AN: 67946

Other (OTH) AF: 0.456 AC: 959 AN: 2102

Alfa AF: 0.496 Hom.: 12913

Bravo AF: 0.410

Asia WGS AF: 0.499 AC: 1732 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.052
DANN	Benign	0.78
PhyloP100		-1.9
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: rs9319427; hg19: chr13-28972164;