chr13-28337683-C-G

Variant names:

• chr13-28337683-C-G
• rs1408245
• NM_002019.4:c.2488+1485G>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.2488+1485G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.173 in 152,158 control chromosomes in the GnomAD database, including 2,389 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 0.17 (2389 hom., cov: 32)
• Consequence: FLT1 NM_002019.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0860
• Publications: 4 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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.207 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FLT1	NM_002019.4	c.2488+1485G>C		intron_variant	Intron 17 of 29	ENST00000282397.9	NP_002010.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FLT1	ENST00000282397.9	c.2488+1485G>C		intron_variant	Intron 17 of 29	1	NM_002019.4	ENSP00000282397.4
FLT1	ENST00000540678.2	n.375+1485G>C		intron_variant	Intron 4 of 16	1
FLT1	ENST00000706527.1	n.313+1485G>C		intron_variant	Intron 3 of 15
ENSG00000298851	ENST00000758418.1	n.285+8908C>G		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.173 AC: 26317 AN: 152040 Hom.: 2385 Cov.: 32

Gnomad AFR AF: 0.210

Gnomad AMI AF: 0.0702

Gnomad AMR AF: 0.126

Gnomad ASJ AF: 0.127

Gnomad EAS AF: 0.179

Gnomad SAS AF: 0.115

Gnomad FIN AF: 0.185

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.167

Gnomad OTH AF: 0.163

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

GnomAD4 genome AF: 0.173 AC: 26339 AN: 152158 Hom.: 2389 Cov.: 32 AF XY: 0.172 AC XY: 12827 AN XY: 74388

African (AFR) AF: 0.210 AC: 8729 AN: 41490

American (AMR) AF: 0.126 AC: 1929 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.127 AC: 440 AN: 3468

East Asian (EAS) AF: 0.179 AC: 927 AN: 5178

South Asian (SAS) AF: 0.115 AC: 554 AN: 4812

European-Finnish (FIN) AF: 0.185 AC: 1960 AN: 10594

Middle Eastern (MID) AF: 0.167 AC: 49 AN: 294

European-Non Finnish (NFE) AF: 0.167 AC: 11343 AN: 68004

Other (OTH) AF: 0.163 AC: 344 AN: 2112

Alfa AF: 0.173 Hom.: 299

Bravo AF: 0.170

Asia WGS AF: 0.123 AC: 429 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.7
DANN	Benign	0.64
PhyloP100		0.086
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: rs1408245; hg19: chr13-28911820;