chr13-28342206-T-C

Variant names:

• chr13-28342206-T-C
• rs2387632
• NM_002019.4:c.2356-2906A>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.2356-2906A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.554 in 152,014 control chromosomes in the GnomAD database, including 25,939 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 0.55 (25939 hom., cov: 31)
• Consequence: FLT1 NM_002019.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.932
• Publications: 15 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.761 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.2356-2906A>G		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.2356-2906A>G		intron	N/A	ENSP00000282397.4
	FLT1	ENST00000540678.2	TSL:1	n.243-2906A>G		intron	N/A
	FLT1	ENST00000706527.1		n.181-2906A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.554 AC: 84140 AN: 151896 Hom.: 25938 Cov.: 31

Gnomad AFR AF: 0.263

Gnomad AMI AF: 0.757

Gnomad AMR AF: 0.569

Gnomad ASJ AF: 0.740

Gnomad EAS AF: 0.782

Gnomad SAS AF: 0.669

Gnomad FIN AF: 0.676

Gnomad MID AF: 0.604

Gnomad NFE AF: 0.670

Gnomad OTH AF: 0.594

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

GnomAD4 genome AF: 0.554 AC: 84156 AN: 152014 Hom.: 25939 Cov.: 31 AF XY: 0.556 AC XY: 41342 AN XY: 74316

African (AFR) AF: 0.262 AC: 10870 AN: 41460

American (AMR) AF: 0.569 AC: 8695 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.740 AC: 2566 AN: 3466

East Asian (EAS) AF: 0.781 AC: 4034 AN: 5162

South Asian (SAS) AF: 0.668 AC: 3222 AN: 4822

European-Finnish (FIN) AF: 0.676 AC: 7141 AN: 10564

Middle Eastern (MID) AF: 0.619 AC: 182 AN: 294

European-Non Finnish (NFE) AF: 0.670 AC: 45500 AN: 67958

Other (OTH) AF: 0.596 AC: 1256 AN: 2108

Alfa AF: 0.641 Hom.: 141844

Bravo AF: 0.535

Asia WGS AF: 0.711 AC: 2469 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.28
DANN	Benign	0.50
PhyloP100		-0.93
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: rs2387632; hg19: chr13-28916343;