13-28307198-T-G

Variant names:

• chr13-28307198-T-G
• rs9554316
• NM_002019.4:c.3721-426A>C

Variant summary

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

The NM_002019.4(FLT1):​c.3721-426A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.695 in 152,028 control chromosomes in the GnomAD database, including 39,735 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 0.69 (39735 hom., cov: 32)
• Consequence: FLT1 NM_002019.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.947
• Publications: 13 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.975 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FLT1	NM_002019.4	c.3721-426A>C		intron_variant	Intron 28 of 29	ENST00000282397.9	NP_002010.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FLT1	ENST00000282397.9	c.3721-426A>C		intron_variant	Intron 28 of 29	1	NM_002019.4	ENSP00000282397.4

Frequencies

GnomAD3 genomes AF: 0.695 AC: 105575 AN: 151910 Hom.: 39711 Cov.: 32

Gnomad AFR AF: 0.381

Gnomad AMI AF: 0.726

Gnomad AMR AF: 0.823

Gnomad ASJ AF: 0.856

Gnomad EAS AF: 0.997

Gnomad SAS AF: 0.898

Gnomad FIN AF: 0.796

Gnomad MID AF: 0.718

Gnomad NFE AF: 0.794

Gnomad OTH AF: 0.740

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

GnomAD4 genome AF: 0.695 AC: 105640 AN: 152028 Hom.: 39735 Cov.: 32 AF XY: 0.705 AC XY: 52362 AN XY: 74286

African (AFR) AF: 0.381 AC: 15785 AN: 41456

American (AMR) AF: 0.823 AC: 12577 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.856 AC: 2969 AN: 3470

East Asian (EAS) AF: 0.997 AC: 5146 AN: 5160

South Asian (SAS) AF: 0.899 AC: 4322 AN: 4810

European-Finnish (FIN) AF: 0.796 AC: 8410 AN: 10568

Middle Eastern (MID) AF: 0.707 AC: 208 AN: 294

European-Non Finnish (NFE) AF: 0.794 AC: 53994 AN: 67972

Other (OTH) AF: 0.743 AC: 1567 AN: 2110

Alfa AF: 0.735 Hom.: 5799

Bravo AF: 0.680

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.5
DANN	Benign	0.36
PhyloP100		0.95
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: rs9554316; hg19: chr13-28881335;