13-28300125-A-G

Variant names:

• chr13-28300125-A-G
• rs9554312
• NM_002019.4:c.*3042T>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.*3042T>C variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.063 in 152,204 control chromosomes in the GnomAD database, including 526 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 0.063 (526 hom., cov: 32)
• Consequence: FLT1 NM_002019.4 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.287
• Publications: 3 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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.307 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FLT1	NM_002019.4	c.*3042T>C		downstream_gene_variant		ENST00000282397.9	NP_002010.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FLT1	ENST00000282397.9	c.*3042T>C		downstream_gene_variant		1	NM_002019.4	ENSP00000282397.4

Frequencies

GnomAD3 genomes AF: 0.0631 AC: 9595 AN: 152086 Hom.: 527 Cov.: 32

Gnomad AFR AF: 0.0391

Gnomad AMI AF: 0.0647

Gnomad AMR AF: 0.0432

Gnomad ASJ AF: 0.0185

Gnomad EAS AF: 0.321

Gnomad SAS AF: 0.0387

Gnomad FIN AF: 0.0959

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0613

Gnomad OTH AF: 0.0630

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

GnomAD4 genome AF: 0.0630 AC: 9595 AN: 152204 Hom.: 526 Cov.: 32 AF XY: 0.0654 AC XY: 4871 AN XY: 74426

African (AFR) AF: 0.0392 AC: 1627 AN: 41522

American (AMR) AF: 0.0432 AC: 660 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0185 AC: 64 AN: 3466

East Asian (EAS) AF: 0.320 AC: 1658 AN: 5178

South Asian (SAS) AF: 0.0387 AC: 187 AN: 4828

European-Finnish (FIN) AF: 0.0959 AC: 1016 AN: 10592

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.0613 AC: 4170 AN: 68002

Other (OTH) AF: 0.0638 AC: 135 AN: 2116

Alfa AF: 0.0610 Hom.: 1157

Bravo AF: 0.0589

Asia WGS AF: 0.148 AC: 512 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.30
DANN	Benign	0.82
PhyloP100		-0.29

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs9554312; hg19: chr13-28874262;