NM_002019.4:c.388+6235G>A

Variant names:

• chr13-28460668-C-T
• rs585421
• NM_002019.4:c.388+6235G>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.388+6235G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.138 in 136,908 control chromosomes in the GnomAD database, including 2,204 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 0.14 (2204 hom., cov: 22)
• Consequence: FLT1 NM_002019.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.207
• Publications: 7 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.319 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FLT1	NM_002019.4	MANE Select	c.388+6235G>A		intron	N/A	NP_002010.2	P17948-1
	FLT1	NM_001160030.2		c.388+6235G>A		intron	N/A	NP_001153502.1	P17948-3
	FLT1	NM_001159920.2		c.388+6235G>A		intron	N/A	NP_001153392.1	P17948-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FLT1	ENST00000282397.9	TSL:1 MANE Select	c.388+6235G>A		intron	N/A	ENSP00000282397.4	P17948-1
	FLT1	ENST00000541932.5	TSL:1	c.388+6235G>A		intron	N/A	ENSP00000437631.1	P17948-3
	FLT1	ENST00000615840.5	TSL:1	c.388+6235G>A		intron	N/A	ENSP00000484039.1	P17948-2

Frequencies

GnomAD3 genomes AF: 0.138 AC: 18875 AN: 136768 Hom.: 2195 Cov.: 22

Gnomad AFR AF: 0.324

Gnomad AMI AF: 0.0900

Gnomad AMR AF: 0.0802

Gnomad ASJ AF: 0.0638

Gnomad EAS AF: 0.00515

Gnomad SAS AF: 0.128

Gnomad FIN AF: 0.0586

Gnomad MID AF: 0.0719

Gnomad NFE AF: 0.0670

Gnomad OTH AF: 0.125

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

GnomAD4 genome AF: 0.138 AC: 18909 AN: 136908 Hom.: 2204 Cov.: 22 AF XY: 0.136 AC XY: 9010 AN XY: 66060

African (AFR) AF: 0.324 AC: 12011 AN: 37084

American (AMR) AF: 0.0798 AC: 1087 AN: 13616

Ashkenazi Jewish (ASJ) AF: 0.0638 AC: 210 AN: 3290

East Asian (EAS) AF: 0.00464 AC: 18 AN: 3880

South Asian (SAS) AF: 0.128 AC: 482 AN: 3778

European-Finnish (FIN) AF: 0.0586 AC: 490 AN: 8366

Middle Eastern (MID) AF: 0.0634 AC: 18 AN: 284

European-Non Finnish (NFE) AF: 0.0670 AC: 4278 AN: 63852

Other (OTH) AF: 0.125 AC: 239 AN: 1914

Alfa AF: 0.0757 Hom.: 1114

Asia WGS AF: 0.0720 AC: 249 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.70
DANN	Benign	0.45
PhyloP100		-0.21
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: rs585421; hg19: chr13-29034805;