rs10507385

Variant names:

• chr13-28422823-T-C
• rs10507385
• NM_002019.4:c.1436+4336A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000282397.9(FLT1):​c.1436+4336A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.19 in 152,178 control chromosomes in the GnomAD database, including 3,252 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 0.19 (3252 hom., cov: 32)
• Consequence: FLT1 ENST00000282397.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.736
• 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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.257 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000282397.9. 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.1436+4336A>G		intron	N/A	NP_002010.2
	FLT1	NM_001160030.2		c.1436+4336A>G		intron	N/A	NP_001153502.1
	FLT1	NM_001159920.2		c.1436+4336A>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.1436+4336A>G		intron	N/A	ENSP00000282397.4
	FLT1	ENST00000541932.5	TSL:1	c.1436+4336A>G		intron	N/A	ENSP00000437631.1
	FLT1	ENST00000615840.5	TSL:1	c.1436+4336A>G		intron	N/A	ENSP00000484039.1

Frequencies

GnomAD3 genomes AF: 0.190 AC: 28953 AN: 152060 Hom.: 3251 Cov.: 32

Gnomad AFR AF: 0.0725

Gnomad AMI AF: 0.380

Gnomad AMR AF: 0.197

Gnomad ASJ AF: 0.273

Gnomad EAS AF: 0.182

Gnomad SAS AF: 0.0791

Gnomad FIN AF: 0.204

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.260

Gnomad OTH AF: 0.200

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

GnomAD4 genome AF: 0.190 AC: 28949 AN: 152178 Hom.: 3252 Cov.: 32 AF XY: 0.185 AC XY: 13763 AN XY: 74392

African (AFR) AF: 0.0725 AC: 3013 AN: 41558

American (AMR) AF: 0.197 AC: 3011 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.273 AC: 948 AN: 3470

East Asian (EAS) AF: 0.182 AC: 944 AN: 5178

South Asian (SAS) AF: 0.0790 AC: 381 AN: 4824

European-Finnish (FIN) AF: 0.204 AC: 2160 AN: 10568

Middle Eastern (MID) AF: 0.231 AC: 68 AN: 294

European-Non Finnish (NFE) AF: 0.260 AC: 17662 AN: 67972

Other (OTH) AF: 0.197 AC: 416 AN: 2112

Alfa AF: 0.233 Hom.: 2505

Bravo AF: 0.187

Asia WGS AF: 0.106 AC: 367 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.52
DANN	Benign	0.61
PhyloP100		-0.74
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: rs10507385; hg19: chr13-28996960;