13-28320932-A-G

Variant names:

• chr13-28320932-A-G
• rs9508016
• NM_002019.4:c.3174+531T>C

Variant summary

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

The NM_002019.4(FLT1):​c.3174+531T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.796 in 151,946 control chromosomes in the GnomAD database, including 48,934 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 0.80 (48934 hom., cov: 30)
• Consequence: FLT1 NM_002019.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0380
• 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.864 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.3174+531T>C		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.3174+531T>C		intron	N/A	ENSP00000282397.4
	FLT1	ENST00000540678.2	TSL:1	n.1061+531T>C		intron	N/A
	FLT1	ENST00000543394.2	TSL:1	n.399+531T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.796 AC: 120844 AN: 151828 Hom.: 48896 Cov.: 30

Gnomad AFR AF: 0.639

Gnomad AMI AF: 0.826

Gnomad AMR AF: 0.806

Gnomad ASJ AF: 0.885

Gnomad EAS AF: 0.882

Gnomad SAS AF: 0.834

Gnomad FIN AF: 0.825

Gnomad MID AF: 0.763

Gnomad NFE AF: 0.870

Gnomad OTH AF: 0.810

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

GnomAD4 genome AF: 0.796 AC: 120938 AN: 151946 Hom.: 48934 Cov.: 30 AF XY: 0.794 AC XY: 58995 AN XY: 74296

African (AFR) AF: 0.639 AC: 26438 AN: 41348

American (AMR) AF: 0.807 AC: 12326 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.885 AC: 3072 AN: 3470

East Asian (EAS) AF: 0.882 AC: 4561 AN: 5170

South Asian (SAS) AF: 0.834 AC: 4011 AN: 4810

European-Finnish (FIN) AF: 0.825 AC: 8720 AN: 10570

Middle Eastern (MID) AF: 0.762 AC: 224 AN: 294

European-Non Finnish (NFE) AF: 0.870 AC: 59121 AN: 67982

Other (OTH) AF: 0.812 AC: 1713 AN: 2110

Alfa AF: 0.847 Hom.: 41288

Bravo AF: 0.786

Asia WGS AF: 0.846 AC: 2941 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.2
DANN	Benign	0.56
PhyloP100		-0.038
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: rs9508016; hg19: chr13-28895069;