13-28439277-G-C

Variant names:

• chr13-28439277-G-C
• rs4771249
• NM_002019.4:c.389-932C>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.389-932C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.78 in 152,108 control chromosomes in the GnomAD database, including 46,473 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 0.78 (46473 hom., cov: 31)
• Consequence: FLT1 NM_002019.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.23
• Publications: 8 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.809 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FLT1	NM_002019.4	MANE Select	c.389-932C>G		intron	N/A	NP_002010.2	P17948-1
	FLT1	NM_001160030.2		c.389-932C>G		intron	N/A	NP_001153502.1	P17948-3
	FLT1	NM_001159920.2		c.389-932C>G		intron	N/A	NP_001153392.1	P17948-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FLT1	ENST00000282397.9	TSL:1 MANE Select	c.389-932C>G		intron	N/A	ENSP00000282397.4	P17948-1
	FLT1	ENST00000541932.5	TSL:1	c.389-932C>G		intron	N/A	ENSP00000437631.1	P17948-3
	FLT1	ENST00000615840.5	TSL:1	c.389-932C>G		intron	N/A	ENSP00000484039.1	P17948-2

Frequencies

GnomAD3 genomes AF: 0.780 AC: 118592 AN: 151990 Hom.: 46447 Cov.: 31

Gnomad AFR AF: 0.816

Gnomad AMI AF: 0.874

Gnomad AMR AF: 0.754

Gnomad ASJ AF: 0.732

Gnomad EAS AF: 0.706

Gnomad SAS AF: 0.599

Gnomad FIN AF: 0.829

Gnomad MID AF: 0.620

Gnomad NFE AF: 0.778

Gnomad OTH AF: 0.751

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

GnomAD4 genome AF: 0.780 AC: 118672 AN: 152108 Hom.: 46473 Cov.: 31 AF XY: 0.775 AC XY: 57646 AN XY: 74360

African (AFR) AF: 0.816 AC: 33835 AN: 41468

American (AMR) AF: 0.753 AC: 11517 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.732 AC: 2540 AN: 3468

East Asian (EAS) AF: 0.705 AC: 3646 AN: 5172

South Asian (SAS) AF: 0.600 AC: 2885 AN: 4810

European-Finnish (FIN) AF: 0.829 AC: 8786 AN: 10592

Middle Eastern (MID) AF: 0.622 AC: 183 AN: 294

European-Non Finnish (NFE) AF: 0.778 AC: 52891 AN: 67990

Other (OTH) AF: 0.752 AC: 1592 AN: 2116

Alfa AF: 0.791 Hom.: 5552

Bravo AF: 0.781

Asia WGS AF: 0.624 AC: 2168 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.76
DANN	Benign	0.30
PhyloP100		-1.2
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: rs4771249; hg19: chr13-29013414;