rs9513070

Positions:

• chr13-28305702-G-A
• chr13-28305702-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002019.4(FLT1):​c.3815+976C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.545 in 152,050 control chromosomes in the GnomAD database, including 23,435 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 (23435 hom., cov: 33)
• Consequence: FLT1 NM_002019.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.66

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.72 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FLT1	NM_002019.4	c.3815+976C>T		intron_variant		ENST00000282397.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FLT1	ENST00000282397.9	c.3815+976C>T		intron_variant		1	NM_002019.4	P1

Frequencies

GnomAD3 genomes AF: 0.546 AC: 82907 AN: 151934 Hom.: 23428 Cov.: 33

Gnomad AFR AF: 0.418

Gnomad AMI AF: 0.601

Gnomad AMR AF: 0.647

Gnomad ASJ AF: 0.681

Gnomad EAS AF: 0.740

Gnomad SAS AF: 0.580

Gnomad FIN AF: 0.452

Gnomad MID AF: 0.513

Gnomad NFE AF: 0.589

Gnomad OTH AF: 0.567

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

GnomAD4 genome AF: 0.545 AC: 82939 AN: 152050 Hom.: 23435 Cov.: 33 AF XY: 0.542 AC XY: 40297 AN XY: 74338

Gnomad4 AFR AF: 0.418

Gnomad4 AMR AF: 0.648

Gnomad4 ASJ AF: 0.681

Gnomad4 EAS AF: 0.739

Gnomad4 SAS AF: 0.579

Gnomad4 FIN AF: 0.452

Gnomad4 NFE AF: 0.589

Gnomad4 OTH AF: 0.568

Alfa AF: 0.580 Hom.: 23122

Bravo AF: 0.558

Asia WGS AF: 0.644 AC: 2238 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.22
DANN	Benign	0.40

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

Publications

LitVar

Other links and lift over

dbSNP: rs9513070; hg19: chr13-28879839;