rs7326277

Variant names:

• chr13-28302077-T-C
• rs7326277
• NM_002019.4:c.*1090A>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.*1090A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.19 in 233,168 control chromosomes in the GnomAD database, including 6,792 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 0.21 (5346 hom., cov: 32)
  • Exomes 𝑓: 0.15 (1446 hom.)
• Consequence: FLT1 NM_002019.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0490
• Publications: 19 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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.457 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.*1090A>G		3_prime_UTR	Exon 30 of 30	NP_002010.2	P17948-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FLT1	ENST00000282397.9	TSL:1 MANE Select	c.*1090A>G		3_prime_UTR	Exon 30 of 30	ENSP00000282397.4	P17948-1
	FLT1	ENST00000909998.1		c.*1090A>G		3_prime_UTR	Exon 30 of 30	ENSP00000580057.1
	FLT1	ENST00000909997.1		c.*1090A>G		3_prime_UTR	Exon 28 of 28	ENSP00000580056.1

Frequencies

GnomAD3 genomes AF: 0.210 AC: 31953 AN: 152008 Hom.: 5335 Cov.: 32

Gnomad AFR AF: 0.462

Gnomad AMI AF: 0.0647

Gnomad AMR AF: 0.121

Gnomad ASJ AF: 0.0732

Gnomad EAS AF: 0.332

Gnomad SAS AF: 0.108

Gnomad FIN AF: 0.127

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.0985

Gnomad OTH AF: 0.177

GnomAD4 exome AF: 0.153 AC: 12403 AN: 81044 Hom.: 1446 Cov.: 0 AF XY: 0.151 AC XY: 5646 AN XY: 37276

African (AFR) AF: 0.462 AC: 1798 AN: 3892

American (AMR) AF: 0.0958 AC: 239 AN: 2496

Ashkenazi Jewish (ASJ) AF: 0.0713 AC: 365 AN: 5118

East Asian (EAS) AF: 0.328 AC: 3734 AN: 11386

South Asian (SAS) AF: 0.115 AC: 81 AN: 702

European-Finnish (FIN) AF: 0.165 AC: 29 AN: 176

Middle Eastern (MID) AF: 0.106 AC: 52 AN: 492

European-Non Finnish (NFE) AF: 0.101 AC: 5075 AN: 50022

Other (OTH) AF: 0.152 AC: 1030 AN: 6760

GnomAD4 genome AF: 0.210 AC: 32010 AN: 152124 Hom.: 5346 Cov.: 32 AF XY: 0.210 AC XY: 15653 AN XY: 74396

African (AFR) AF: 0.462 AC: 19145 AN: 41436

American (AMR) AF: 0.120 AC: 1841 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0732 AC: 254 AN: 3472

East Asian (EAS) AF: 0.332 AC: 1716 AN: 5176

South Asian (SAS) AF: 0.108 AC: 522 AN: 4832

European-Finnish (FIN) AF: 0.127 AC: 1348 AN: 10596

Middle Eastern (MID) AF: 0.170 AC: 50 AN: 294

European-Non Finnish (NFE) AF: 0.0985 AC: 6697 AN: 67996

Other (OTH) AF: 0.179 AC: 378 AN: 2116

Alfa AF: 0.154 Hom.: 1368

Bravo AF: 0.221

Asia WGS AF: 0.225 AC: 785 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.7
DANN	Benign	0.65
PhyloP100		-0.049
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: rs7326277; hg19: chr13-28876214;