13-28486462-T-G

Variant names:

• chr13-28486462-T-G
• rs748253
• NM_002019.4:c.64+8318A>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.64+8318A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.586 in 152,082 control chromosomes in the GnomAD database, including 26,997 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 0.59 (26997 hom., cov: 34)
• Consequence: FLT1 NM_002019.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.890
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.708 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+8318A>C		intron	N/A	NP_002010.2
	FLT1	NM_001160030.2		c.64+8318A>C		intron	N/A	NP_001153502.1
	FLT1	NM_001159920.2		c.64+8318A>C		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+8318A>C		intron	N/A	ENSP00000282397.4
	FLT1	ENST00000541932.5	TSL:1	c.64+8318A>C		intron	N/A	ENSP00000437631.1
	FLT1	ENST00000615840.5	TSL:1	c.64+8318A>C		intron	N/A	ENSP00000484039.1

Frequencies

GnomAD3 genomes AF: 0.586 AC: 89102 AN: 151964 Hom.: 26988 Cov.: 34

Gnomad AFR AF: 0.437

Gnomad AMI AF: 0.691

Gnomad AMR AF: 0.719

Gnomad ASJ AF: 0.683

Gnomad EAS AF: 0.653

Gnomad SAS AF: 0.701

Gnomad FIN AF: 0.502

Gnomad MID AF: 0.639

Gnomad NFE AF: 0.639

Gnomad OTH AF: 0.634

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

GnomAD4 genome AF: 0.586 AC: 89147 AN: 152082 Hom.: 26997 Cov.: 34 AF XY: 0.587 AC XY: 43651 AN XY: 74356

African (AFR) AF: 0.437 AC: 18135 AN: 41484

American (AMR) AF: 0.719 AC: 10995 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.683 AC: 2369 AN: 3470

East Asian (EAS) AF: 0.654 AC: 3381 AN: 5168

South Asian (SAS) AF: 0.700 AC: 3370 AN: 4816

European-Finnish (FIN) AF: 0.502 AC: 5310 AN: 10576

Middle Eastern (MID) AF: 0.633 AC: 186 AN: 294

European-Non Finnish (NFE) AF: 0.639 AC: 43434 AN: 67960

Other (OTH) AF: 0.632 AC: 1337 AN: 2114

Alfa AF: 0.604 Hom.: 8868

Bravo AF: 0.596

Asia WGS AF: 0.673 AC: 2342 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.79
DANN	Benign	0.38
PhyloP100		-0.89
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: rs748253; hg19: chr13-29060599;