13-28355574-A-G

Variant names:

• chr13-28355574-A-G
• rs17086609
• NM_002019.4:c.2248+1980T>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.2248+1980T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.269 in 152,138 control chromosomes in the GnomAD database, including 6,783 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 0.27 (6783 hom., cov: 32)
• Consequence: FLT1 NM_002019.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.514
• Publications: 19 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]

ENSG00000298851 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.469 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002019.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FLT1	NM_002019.4	MANE Select	c.2248+1980T>C		intron	N/A	NP_002010.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FLT1	ENST00000282397.9	TSL:1 MANE Select	c.2248+1980T>C		intron	N/A	ENSP00000282397.4
	ENSG00000298851	ENST00000758418.1		n.286-2322A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.269 AC: 40864 AN: 152020 Hom.: 6781 Cov.: 32

Gnomad AFR AF: 0.0745

Gnomad AMI AF: 0.398

Gnomad AMR AF: 0.299

Gnomad ASJ AF: 0.421

Gnomad EAS AF: 0.484

Gnomad SAS AF: 0.474

Gnomad FIN AF: 0.369

Gnomad MID AF: 0.313

Gnomad NFE AF: 0.323

Gnomad OTH AF: 0.308

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

GnomAD4 genome AF: 0.269 AC: 40874 AN: 152138 Hom.: 6783 Cov.: 32 AF XY: 0.275 AC XY: 20456 AN XY: 74374

African (AFR) AF: 0.0743 AC: 3088 AN: 41544

American (AMR) AF: 0.300 AC: 4583 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.421 AC: 1461 AN: 3470

East Asian (EAS) AF: 0.485 AC: 2502 AN: 5158

South Asian (SAS) AF: 0.474 AC: 2285 AN: 4818

European-Finnish (FIN) AF: 0.369 AC: 3897 AN: 10570

Middle Eastern (MID) AF: 0.333 AC: 98 AN: 294

European-Non Finnish (NFE) AF: 0.323 AC: 21959 AN: 67974

Other (OTH) AF: 0.303 AC: 638 AN: 2106

Alfa AF: 0.317 Hom.: 27164

Bravo AF: 0.256

Asia WGS AF: 0.432 AC: 1504 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.7
DANN	Benign	0.61
PhyloP100		0.51
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: rs17086609; hg19: chr13-28929711;