13-28471715-A-G

Variant names:

• chr13-28471715-A-G
• rs2256849
• NM_002019.4:c.65-4098T>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.65-4098T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.257 in 152,072 control chromosomes in the GnomAD database, including 7,202 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 (7202 hom., cov: 32)
• Consequence: FLT1 NM_002019.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0690
• Publications: 6 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 = 0.502 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FLT1	NM_002019.4	MANE Select	c.65-4098T>C		intron	N/A	NP_002010.2	P17948-1
	FLT1	NM_001160030.2		c.65-4098T>C		intron	N/A	NP_001153502.1	P17948-3
	FLT1	NM_001159920.2		c.65-4098T>C		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.65-4098T>C		intron	N/A	ENSP00000282397.4	P17948-1
	FLT1	ENST00000541932.5	TSL:1	c.65-4098T>C		intron	N/A	ENSP00000437631.1	P17948-3
	FLT1	ENST00000615840.5	TSL:1	c.65-4098T>C		intron	N/A	ENSP00000484039.1	P17948-2

Frequencies

GnomAD3 genomes AF: 0.257 AC: 39064 AN: 151954 Hom.: 7170 Cov.: 32

Gnomad AFR AF: 0.507

Gnomad AMI AF: 0.101

Gnomad AMR AF: 0.281

Gnomad ASJ AF: 0.118

Gnomad EAS AF: 0.0468

Gnomad SAS AF: 0.197

Gnomad FIN AF: 0.146

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.148

Gnomad OTH AF: 0.234

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

GnomAD4 genome AF: 0.257 AC: 39144 AN: 152072 Hom.: 7202 Cov.: 32 AF XY: 0.255 AC XY: 18939 AN XY: 74328

African (AFR) AF: 0.508 AC: 21028 AN: 41406

American (AMR) AF: 0.281 AC: 4297 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.118 AC: 408 AN: 3466

East Asian (EAS) AF: 0.0467 AC: 242 AN: 5178

South Asian (SAS) AF: 0.198 AC: 952 AN: 4818

European-Finnish (FIN) AF: 0.146 AC: 1550 AN: 10584

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.148 AC: 10045 AN: 68014

Other (OTH) AF: 0.233 AC: 492 AN: 2114

Alfa AF: 0.160 Hom.: 1238

Bravo AF: 0.278

Asia WGS AF: 0.143 AC: 500 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	3.2
DANN	Benign	0.76
PhyloP100		-0.069
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: rs2256849; hg19: chr13-29045852;