NM_002019.4:c.1660+2454C>G

Variant names:

• chr13-28394506-G-C
• rs10507383
• NM_002019.4:c.1660+2454C>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.1660+2454C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.107 in 152,170 control chromosomes in the GnomAD database, including 1,017 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 0.11 (1017 hom., cov: 31)
• Consequence: FLT1 NM_002019.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.273
• Publications: 2 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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.161 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FLT1	NM_002019.4	c.1660+2454C>G		intron_variant	Intron 12 of 29	ENST00000282397.9	NP_002010.2
FLT1	NM_001160030.2	c.1660+2454C>G		intron_variant	Intron 12 of 14		NP_001153502.1
FLT1	NM_001159920.2	c.1660+2454C>G		intron_variant	Intron 12 of 12		NP_001153392.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FLT1	ENST00000282397.9	c.1660+2454C>G		intron_variant	Intron 12 of 29	1	NM_002019.4	ENSP00000282397.4

Frequencies

GnomAD3 genomes AF: 0.107 AC: 16200 AN: 152052 Hom.: 1011 Cov.: 31

Gnomad AFR AF: 0.164

Gnomad AMI AF: 0.0910

Gnomad AMR AF: 0.0793

Gnomad ASJ AF: 0.0634

Gnomad EAS AF: 0.00461

Gnomad SAS AF: 0.107

Gnomad FIN AF: 0.0930

Gnomad MID AF: 0.0955

Gnomad NFE AF: 0.0901

Gnomad OTH AF: 0.102

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

GnomAD4 genome AF: 0.107 AC: 16215 AN: 152170 Hom.: 1017 Cov.: 31 AF XY: 0.107 AC XY: 7974 AN XY: 74392

African (AFR) AF: 0.164 AC: 6811 AN: 41496

American (AMR) AF: 0.0790 AC: 1208 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0634 AC: 220 AN: 3468

East Asian (EAS) AF: 0.00424 AC: 22 AN: 5192

South Asian (SAS) AF: 0.108 AC: 518 AN: 4808

European-Finnish (FIN) AF: 0.0930 AC: 986 AN: 10598

Middle Eastern (MID) AF: 0.0822 AC: 24 AN: 292

European-Non Finnish (NFE) AF: 0.0901 AC: 6126 AN: 67998

Other (OTH) AF: 0.103 AC: 217 AN: 2114

Alfa AF: 0.104 Hom.: 120

Bravo AF: 0.106

Asia WGS AF: 0.0570 AC: 201 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.2
DANN	Benign	0.46
PhyloP100		-0.27
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: rs10507383; hg19: chr13-28968643;