chr13-28396780-C-T

Variant names:

• chr13-28396780-C-T
• rs7990486
• NM_002019.4:c.1660+180G>A

Variant summary

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

The NM_002019.4(FLT1):​c.1660+180G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.977 in 695,840 control chromosomes in the GnomAD database, including 332,786 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 0.95 (68947 hom., cov: 29)
  • Exomes 𝑓: 0.98 (263839 hom.)
• Consequence: FLT1 NM_002019.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.298
• Publications: 2 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 (EAS) allele frequency at 95% confidence interval = 0.982 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FLT1	NM_002019.4	c.1660+180G>A		intron_variant	Intron 12 of 29	ENST00000282397.9	NP_002010.2
FLT1	NM_001160030.2	c.1660+180G>A		intron_variant	Intron 12 of 14		NP_001153502.1
FLT1	NM_001159920.2	c.1660+180G>A		intron_variant	Intron 12 of 12		NP_001153392.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FLT1	ENST00000282397.9	c.1660+180G>A		intron_variant	Intron 12 of 29	1	NM_002019.4	ENSP00000282397.4

Frequencies

GnomAD3 genomes AF: 0.950 AC: 144391 AN: 151960 Hom.: 68907 Cov.: 29

Gnomad AFR AF: 0.851

Gnomad AMI AF: 0.996

Gnomad AMR AF: 0.975

Gnomad ASJ AF: 0.989

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.979

Gnomad FIN AF: 0.998

Gnomad MID AF: 0.965

Gnomad NFE AF: 0.988

Gnomad OTH AF: 0.963

GnomAD2 exomes AF: 0.981 AC: 134139 AN: 136722 AF XY: 0.983

Gnomad AFR exome AF: 0.854

Gnomad AMR exome AF: 0.987

Gnomad ASJ exome AF: 0.986

Gnomad EAS exome AF: 1.00

Gnomad FIN exome AF: 0.999

Gnomad NFE exome AF: 0.988

Gnomad OTH exome AF: 0.981

GnomAD4 exome AF: 0.985 AC: 535502 AN: 543762 Hom.: 263839 Cov.: 3 AF XY: 0.985 AC XY: 290542 AN XY: 294836

African (AFR) AF: 0.860 AC: 13384 AN: 15566

American (AMR) AF: 0.985 AC: 33905 AN: 34434

Ashkenazi Jewish (ASJ) AF: 0.986 AC: 19502 AN: 19776

East Asian (EAS) AF: 1.00 AC: 31730 AN: 31730

South Asian (SAS) AF: 0.985 AC: 60850 AN: 61796

European-Finnish (FIN) AF: 0.998 AC: 34179 AN: 34238

Middle Eastern (MID) AF: 0.974 AC: 3884 AN: 3988

European-Non Finnish (NFE) AF: 0.989 AC: 308636 AN: 312154

Other (OTH) AF: 0.978 AC: 29432 AN: 30080

GnomAD4 genome AF: 0.950 AC: 144490 AN: 152078 Hom.: 68947 Cov.: 29 AF XY: 0.952 AC XY: 70759 AN XY: 74354

African (AFR) AF: 0.851 AC: 35262 AN: 41424

American (AMR) AF: 0.975 AC: 14883 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.989 AC: 3433 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5172 AN: 5172

South Asian (SAS) AF: 0.979 AC: 4702 AN: 4802

European-Finnish (FIN) AF: 0.998 AC: 10584 AN: 10606

Middle Eastern (MID) AF: 0.966 AC: 284 AN: 294

European-Non Finnish (NFE) AF: 0.988 AC: 67230 AN: 68020

Other (OTH) AF: 0.963 AC: 2032 AN: 2110

Alfa AF: 0.960 Hom.: 14493

Bravo AF: 0.944

Asia WGS AF: 0.978 AC: 3401 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.8
DANN	Benign	0.66
PhyloP100		-0.30
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: rs7990486; hg19: chr13-28970917;