chr13-28422915-C-T

Variant names:

• chr13-28422915-C-T
• rs722503
• NM_002019.4:c.1436+4244G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002019.4(FLT1):​c.1436+4244G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.744 in 152,008 control chromosomes in the GnomAD database, including 42,251 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 0.74 (42251 hom., cov: 31)
• Consequence: FLT1 NM_002019.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.119
• Publications: 28 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=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.747 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FLT1	NM_002019.4	c.1436+4244G>A		intron_variant	Intron 10 of 29	ENST00000282397.9	NP_002010.2
FLT1	NM_001160030.2	c.1436+4244G>A		intron_variant	Intron 10 of 14		NP_001153502.1
FLT1	NM_001159920.2	c.1436+4244G>A		intron_variant	Intron 10 of 12		NP_001153392.1
FLT1	NM_001160031.1	c.1436+4244G>A		intron_variant	Intron 10 of 11		NP_001153503.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FLT1	ENST00000282397.9	c.1436+4244G>A		intron_variant	Intron 10 of 29	1	NM_002019.4	ENSP00000282397.4

Frequencies

GnomAD3 genomes AF: 0.745 AC: 113094 AN: 151892 Hom.: 42236 Cov.: 31

Gnomad AFR AF: 0.748

Gnomad AMI AF: 0.841

Gnomad AMR AF: 0.736

Gnomad ASJ AF: 0.689

Gnomad EAS AF: 0.713

Gnomad SAS AF: 0.597

Gnomad FIN AF: 0.795

Gnomad MID AF: 0.595

Gnomad NFE AF: 0.752

Gnomad OTH AF: 0.716

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

GnomAD4 genome AF: 0.744 AC: 113162 AN: 152008 Hom.: 42251 Cov.: 31 AF XY: 0.741 AC XY: 55074 AN XY: 74288

African (AFR) AF: 0.748 AC: 31001 AN: 41448

American (AMR) AF: 0.735 AC: 11222 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.689 AC: 2389 AN: 3468

East Asian (EAS) AF: 0.712 AC: 3676 AN: 5166

South Asian (SAS) AF: 0.598 AC: 2869 AN: 4796

European-Finnish (FIN) AF: 0.795 AC: 8389 AN: 10556

Middle Eastern (MID) AF: 0.595 AC: 175 AN: 294

European-Non Finnish (NFE) AF: 0.753 AC: 51161 AN: 67986

Other (OTH) AF: 0.716 AC: 1513 AN: 2114

Alfa AF: 0.740 Hom.: 23403

Bravo AF: 0.743

Asia WGS AF: 0.613 AC: 2134 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	6.1
DANN	Benign	0.67
PhyloP100		-0.12
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: rs722503; hg19: chr13-28997052;