NM_002019.4:c.3387-692T>G

Variant names:

• chr13-28312790-A-C
• rs9554320
• NM_002019.4:c.3387-692T>G

Variant summary

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

The NM_002019.4(FLT1):​c.3387-692T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.509 in 151,716 control chromosomes in the GnomAD database, including 22,342 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 0.51 (22342 hom., cov: 29)
• Consequence: FLT1 NM_002019.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.751
• Publications: 31 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]

LOC124903141 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.754 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FLT1	NM_002019.4	c.3387-692T>G		intron_variant	Intron 25 of 29	ENST00000282397.9	NP_002010.2
LOC124903141	XR_007063736.1	n.30A>C		non_coding_transcript_exon_variant	Exon 1 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FLT1	ENST00000282397.9	c.3387-692T>G		intron_variant	Intron 25 of 29	1	NM_002019.4	ENSP00000282397.4

Frequencies

GnomAD3 genomes AF: 0.509 AC: 77172 AN: 151598 Hom.: 22321 Cov.: 29

Gnomad AFR AF: 0.224

Gnomad AMI AF: 0.606

Gnomad AMR AF: 0.668

Gnomad ASJ AF: 0.653

Gnomad EAS AF: 0.773

Gnomad SAS AF: 0.741

Gnomad FIN AF: 0.639

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.581

Gnomad OTH AF: 0.545

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

GnomAD4 genome AF: 0.509 AC: 77207 AN: 151716 Hom.: 22342 Cov.: 29 AF XY: 0.520 AC XY: 38522 AN XY: 74140

African (AFR) AF: 0.223 AC: 9243 AN: 41400

American (AMR) AF: 0.669 AC: 10188 AN: 15222

Ashkenazi Jewish (ASJ) AF: 0.653 AC: 2263 AN: 3468

East Asian (EAS) AF: 0.774 AC: 3968 AN: 5126

South Asian (SAS) AF: 0.741 AC: 3547 AN: 4786

European-Finnish (FIN) AF: 0.639 AC: 6710 AN: 10502

Middle Eastern (MID) AF: 0.473 AC: 138 AN: 292

European-Non Finnish (NFE) AF: 0.581 AC: 39454 AN: 67918

Other (OTH) AF: 0.547 AC: 1146 AN: 2094

Alfa AF: 0.547 Hom.: 23604

Bravo AF: 0.497

Asia WGS AF: 0.717 AC: 2493 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.8
DANN	Benign	0.50
PhyloP100		0.75
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: rs9554320; hg19: chr13-28886927;