chr13-28465077-T-C

Variant names:

• chr13-28465077-T-C
• rs622227
• NM_002019.4:c.388+1826A>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.388+1826A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.258 in 152,104 control chromosomes in the GnomAD database, including 7,189 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 0.26 (7189 hom., cov: 32)
• Consequence: FLT1 NM_002019.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.717
• Publications: 11 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 (AFR) allele frequency at 95% confidence interval = 0.502 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.388+1826A>G		intron	N/A	NP_002010.2
	FLT1	NM_001160030.2		c.388+1826A>G		intron	N/A	NP_001153502.1
	FLT1	NM_001159920.2		c.388+1826A>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.388+1826A>G		intron	N/A	ENSP00000282397.4
	FLT1	ENST00000541932.5	TSL:1	c.388+1826A>G		intron	N/A	ENSP00000437631.1
	FLT1	ENST00000615840.5	TSL:1	c.388+1826A>G		intron	N/A	ENSP00000484039.1

Frequencies

GnomAD3 genomes AF: 0.257 AC: 39107 AN: 151986 Hom.: 7160 Cov.: 32

Gnomad AFR AF: 0.507

Gnomad AMI AF: 0.101

Gnomad AMR AF: 0.282

Gnomad ASJ AF: 0.119

Gnomad EAS AF: 0.0462

Gnomad SAS AF: 0.196

Gnomad FIN AF: 0.147

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.148

Gnomad OTH AF: 0.235

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

GnomAD4 genome AF: 0.258 AC: 39186 AN: 152104 Hom.: 7189 Cov.: 32 AF XY: 0.256 AC XY: 19010 AN XY: 74380

African (AFR) AF: 0.508 AC: 21036 AN: 41434

American (AMR) AF: 0.282 AC: 4303 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.119 AC: 412 AN: 3470

East Asian (EAS) AF: 0.0461 AC: 239 AN: 5186

South Asian (SAS) AF: 0.196 AC: 948 AN: 4830

European-Finnish (FIN) AF: 0.147 AC: 1561 AN: 10596

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.148 AC: 10064 AN: 67998

Other (OTH) AF: 0.234 AC: 494 AN: 2108

Alfa AF: 0.180 Hom.: 5225

Bravo AF: 0.278

Asia WGS AF: 0.143 AC: 498 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	0.74
DANN	Benign	0.38
PhyloP100		-0.72
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: rs622227; hg19: chr13-29039214;