rs6877011

chr5-180602471-C-G

Variant summary

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

The NM_182925.5(FLT4):c.*721G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0999 in 397,128 control chromosomes in the GnomAD database, including 3,641 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 0.10 (1187 hom., cov: 32)
  • Exomes 𝑓: 0.099 (2454 hom.)
• Consequence: FLT4 NM_182925.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.529

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=-0.5).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.375 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FLT4	NM_182925.5	c.*721G>C		3_prime_UTR_variant	30/30	ENST00000261937.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FLT4	ENST00000261937.11	c.*721G>C		3_prime_UTR_variant	30/30	1	NM_182925.5	P1

Frequencies

GnomAD3 genomes AF: 0.101 AC: 15354 AN: 152108 Hom.: 1181 Cov.: 32

Gnomad AFR AF: 0.152

Gnomad AMI AF: 0.0197

Gnomad AMR AF: 0.0629

Gnomad ASJ AF: 0.119

Gnomad EAS AF: 0.389

Gnomad SAS AF: 0.145

Gnomad FIN AF: 0.0753

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.0575

Gnomad OTH AF: 0.0961

GnomAD4 exome AF: 0.0992 AC: 24302 AN: 244904 Hom.: 2454 Cov.: 0 AF XY: 0.0978 AC XY: 12149 AN XY: 124182

Gnomad4 AFR exome AF: 0.155

Gnomad4 AMR exome AF: 0.0627

Gnomad4 ASJ exome AF: 0.118

Gnomad4 EAS exome AF: 0.399

Gnomad4 SAS exome AF: 0.151

Gnomad4 FIN exome AF: 0.0677

Gnomad4 NFE exome AF: 0.0579

Gnomad4 OTH exome AF: 0.0943

GnomAD4 genome AF: 0.101 AC: 15372 AN: 152224 Hom.: 1187 Cov.: 32 AF XY: 0.103 AC XY: 7681 AN XY: 74420

Gnomad4 AFR AF: 0.152

Gnomad4 AMR AF: 0.0628

Gnomad4 ASJ AF: 0.119

Gnomad4 EAS AF: 0.389

Gnomad4 SAS AF: 0.144

Gnomad4 FIN AF: 0.0753

Gnomad4 NFE AF: 0.0575

Gnomad4 OTH AF: 0.104

Alfa AF: 0.0778 Hom.: 83

Bravo AF: 0.106

Asia WGS AF: 0.268 AC: 935 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
Cadd	Benign	4.3
Dann	Benign	0.78

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: rs6877011; hg19: chr5-180029471; COSMIC: COSV56128143; COSMIC: COSV56128143;