rs12858139

Variant names:

• chr13-28483931-A-C
• rs12858139
• NM_002019.4:c.64+10849T>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.64+10849T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.448 in 152,018 control chromosomes in the GnomAD database, including 17,386 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 0.45 (17386 hom., cov: 32)
• Consequence: FLT1 NM_002019.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00800
• Publications: 8 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=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.613 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.64+10849T>G		intron	N/A	NP_002010.2
	FLT1	NM_001160030.2		c.64+10849T>G		intron	N/A	NP_001153502.1
	FLT1	NM_001159920.2		c.64+10849T>G		intron	N/A	NP_001153392.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FLT1	ENST00000282397.9	TSL:1 MANE Select	c.64+10849T>G		intron	N/A	ENSP00000282397.4
	FLT1	ENST00000541932.5	TSL:1	c.64+10849T>G		intron	N/A	ENSP00000437631.1
	FLT1	ENST00000615840.5	TSL:1	c.64+10849T>G		intron	N/A	ENSP00000484039.1

Frequencies

GnomAD3 genomes AF: 0.449 AC: 68133 AN: 151902 Hom.: 17389 Cov.: 32

Gnomad AFR AF: 0.192

Gnomad AMI AF: 0.685

Gnomad AMR AF: 0.512

Gnomad ASJ AF: 0.632

Gnomad EAS AF: 0.570

Gnomad SAS AF: 0.633

Gnomad FIN AF: 0.411

Gnomad MID AF: 0.589

Gnomad NFE AF: 0.559

Gnomad OTH AF: 0.514

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

GnomAD4 genome AF: 0.448 AC: 68132 AN: 152018 Hom.: 17386 Cov.: 32 AF XY: 0.448 AC XY: 33317 AN XY: 74310

African (AFR) AF: 0.191 AC: 7944 AN: 41492

American (AMR) AF: 0.512 AC: 7823 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.632 AC: 2190 AN: 3466

East Asian (EAS) AF: 0.570 AC: 2948 AN: 5168

South Asian (SAS) AF: 0.632 AC: 3042 AN: 4814

European-Finnish (FIN) AF: 0.411 AC: 4327 AN: 10540

Middle Eastern (MID) AF: 0.583 AC: 169 AN: 290

European-Non Finnish (NFE) AF: 0.559 AC: 37981 AN: 67954

Other (OTH) AF: 0.513 AC: 1083 AN: 2110

Alfa AF: 0.495 Hom.: 4804

Bravo AF: 0.442

Asia WGS AF: 0.587 AC: 2043 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.3
DANN	Benign	0.58
PhyloP100		0.0080
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: rs12858139; hg19: chr13-29058068;