rs7995976

Variant names:

• chr13-28366923-A-C
• rs7995976
• NM_002019.4:c.2117-9238T>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.2117-9238T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.698 in 152,044 control chromosomes in the GnomAD database, including 37,725 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 0.70 (37725 hom., cov: 32)
• Consequence: FLT1 NM_002019.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.340
• Publications: 17 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=-0.98).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.77 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FLT1	NM_002019.4	c.2117-9238T>G		intron_variant	Intron 14 of 29	ENST00000282397.9	NP_002010.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FLT1	ENST00000282397.9	c.2117-9238T>G		intron_variant	Intron 14 of 29	1	NM_002019.4	ENSP00000282397.4

Frequencies

GnomAD3 genomes AF: 0.698 AC: 106117 AN: 151926 Hom.: 37700 Cov.: 32

Gnomad AFR AF: 0.555

Gnomad AMI AF: 0.852

Gnomad AMR AF: 0.782

Gnomad ASJ AF: 0.815

Gnomad EAS AF: 0.677

Gnomad SAS AF: 0.759

Gnomad FIN AF: 0.697

Gnomad MID AF: 0.763

Gnomad NFE AF: 0.755

Gnomad OTH AF: 0.722

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

GnomAD4 genome AF: 0.698 AC: 106190 AN: 152044 Hom.: 37725 Cov.: 32 AF XY: 0.699 AC XY: 51937 AN XY: 74324

African (AFR) AF: 0.555 AC: 23010 AN: 41442

American (AMR) AF: 0.782 AC: 11959 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.815 AC: 2828 AN: 3472

East Asian (EAS) AF: 0.678 AC: 3499 AN: 5164

South Asian (SAS) AF: 0.759 AC: 3658 AN: 4822

European-Finnish (FIN) AF: 0.697 AC: 7358 AN: 10562

Middle Eastern (MID) AF: 0.776 AC: 228 AN: 294

European-Non Finnish (NFE) AF: 0.755 AC: 51350 AN: 67972

Other (OTH) AF: 0.720 AC: 1523 AN: 2114

Alfa AF: 0.747 Hom.: 90725

Bravo AF: 0.699

Asia WGS AF: 0.732 AC: 2545 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	2.9
DANN	Benign	0.52
PhyloP100		-0.34
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs7995976; hg19: chr13-28941060;