rs2279622

Positions:

• chr5-180601743-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_182925.5(FLT4):​c.*1449G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.123 in 232,694 control chromosomes in the GnomAD database, including 2,802 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 0.13 (2218 hom., cov: 32)
  • Exomes 𝑓: 0.10 (584 hom.)
• Consequence: FLT4 NM_182925.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.389

Genes affected

FLT4 (HGNC:3767): (fms related receptor tyrosine kinase 4) This gene encodes a tyrosine kinase receptor for vascular endothelial growth factors C and D. The protein is thought to be involved in lymphangiogenesis and maintenance of the lymphatic endothelium. Mutations in this gene cause hereditary lymphedema type IA. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.292 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FLT4	NM_182925.5	c.*1449G>A		3_prime_UTR_variant	30/30	ENST00000261937.11	NP_891555.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FLT4	ENST00000261937.11	c.*1449G>A		3_prime_UTR_variant	30/30	1	NM_182925.5	ENSP00000261937	P1

Frequencies

GnomAD3 genomes AF: 0.134 AC: 20391 AN: 151828 Hom.: 2212 Cov.: 32

Gnomad AFR AF: 0.297

Gnomad AMI AF: 0.00768

Gnomad AMR AF: 0.0689

Gnomad ASJ AF: 0.0833

Gnomad EAS AF: 0.203

Gnomad SAS AF: 0.132

Gnomad FIN AF: 0.0527

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0631

Gnomad OTH AF: 0.116

GnomAD4 exome AF: 0.101 AC: 8175 AN: 80750 Hom.: 584 Cov.: 0 AF XY: 0.101 AC XY: 3732 AN XY: 37116

Gnomad4 AFR exome AF: 0.307

Gnomad4 AMR exome AF: 0.0637

Gnomad4 ASJ exome AF: 0.0811

Gnomad4 EAS exome AF: 0.206

Gnomad4 SAS exome AF: 0.163

Gnomad4 FIN exome AF: 0.0875

Gnomad4 NFE exome AF: 0.0655

Gnomad4 OTH exome AF: 0.0941

GnomAD4 genome AF: 0.134 AC: 20421 AN: 151944 Hom.: 2218 Cov.: 32 AF XY: 0.134 AC XY: 9922 AN XY: 74282

Gnomad4 AFR AF: 0.297

Gnomad4 AMR AF: 0.0686

Gnomad4 ASJ AF: 0.0833

Gnomad4 EAS AF: 0.202

Gnomad4 SAS AF: 0.131

Gnomad4 FIN AF: 0.0527

Gnomad4 NFE AF: 0.0631

Gnomad4 OTH AF: 0.117

Alfa AF: 0.0759 Hom.: 612

Bravo AF: 0.143

Asia WGS AF: 0.183 AC: 640 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.1
DANN	Benign	0.72

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

Publications

LitVar

Other links and lift over

dbSNP: rs2279622; hg19: chr5-180028743;