chr5-180601717-T-C

Position:

• chr5-180601717-T-C

Variant summary

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

The NM_182925.5(FLT4):​c.*1475A>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 0.79 in 233,120 control chromosomes in the GnomAD database, including 75,327 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 0.77 (47018 hom., cov: 31)
  • Exomes 𝑓: 0.83 (28309 hom.)
• Consequence: FLT4 NM_182925.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.05

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=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.894 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FLT4	NM_182925.5	c.*1475A>G		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	c.*1475A>G		3_prime_UTR_variant	30/30	1	NM_182925.5	ENSP00000261937.6

Frequencies

GnomAD3 genomes AF: 0.770 AC: 116932 AN: 151902 Hom.: 46990 Cov.: 31

Gnomad AFR AF: 0.535

Gnomad AMI AF: 0.922

Gnomad AMR AF: 0.746

Gnomad ASJ AF: 0.856

Gnomad EAS AF: 0.667

Gnomad SAS AF: 0.770

Gnomad FIN AF: 0.892

Gnomad MID AF: 0.820

Gnomad NFE AF: 0.899

Gnomad OTH AF: 0.778

GnomAD4 exome AF: 0.827 AC: 67065 AN: 81100 Hom.: 28309 Cov.: 0 AF XY: 0.830 AC XY: 30957 AN XY: 37290

Gnomad4 AFR exome AF: 0.523

Gnomad4 AMR exome AF: 0.726

Gnomad4 ASJ exome AF: 0.858

Gnomad4 EAS exome AF: 0.613

Gnomad4 SAS exome AF: 0.750

Gnomad4 FIN exome AF: 0.871

Gnomad4 NFE exome AF: 0.901

Gnomad4 OTH exome AF: 0.839

GnomAD4 genome AF: 0.770 AC: 117003 AN: 152020 Hom.: 47018 Cov.: 31 AF XY: 0.769 AC XY: 57146 AN XY: 74304

Gnomad4 AFR AF: 0.535

Gnomad4 AMR AF: 0.746

Gnomad4 ASJ AF: 0.856

Gnomad4 EAS AF: 0.668

Gnomad4 SAS AF: 0.770

Gnomad4 FIN AF: 0.892

Gnomad4 NFE AF: 0.899

Gnomad4 OTH AF: 0.777

Alfa AF: 0.839 Hom.: 22847

Bravo AF: 0.749

Asia WGS AF: 0.697 AC: 2423 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.16
DANN	Benign	0.23

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: rs307822; hg19: chr5-180028717;