5-180638103-C-T

Position:

• chr5-180638103-C-T

Variant summary

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

The ENST00000261937.11(FLT4):​c.59-6325G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.842 in 152,008 control chromosomes in the GnomAD database, including 54,662 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 0.84 (54662 hom., cov: 31)
• Consequence: FLT4 ENST00000261937.11 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.75

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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.957 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FLT4	NM_182925.5	c.59-6325G>A		intron_variant		ENST00000261937.11	NP_891555.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FLT4	ENST00000261937.11	c.59-6325G>A		intron_variant		1	NM_182925.5	ENSP00000261937	P1

Frequencies

GnomAD3 genomes AF: 0.842 AC: 127938 AN: 151890 Hom.: 54630 Cov.: 31

Gnomad AFR AF: 0.686

Gnomad AMI AF: 0.719

Gnomad AMR AF: 0.907

Gnomad ASJ AF: 0.894

Gnomad EAS AF: 0.979

Gnomad SAS AF: 0.914

Gnomad FIN AF: 0.915

Gnomad MID AF: 0.899

Gnomad NFE AF: 0.894

Gnomad OTH AF: 0.863

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.842 AC: 128021 AN: 152008 Hom.: 54662 Cov.: 31 AF XY: 0.846 AC XY: 62882 AN XY: 74300

Gnomad4 AFR AF: 0.686

Gnomad4 AMR AF: 0.908

Gnomad4 ASJ AF: 0.894

Gnomad4 EAS AF: 0.980

Gnomad4 SAS AF: 0.914

Gnomad4 FIN AF: 0.915

Gnomad4 NFE AF: 0.894

Gnomad4 OTH AF: 0.864

Alfa AF: 0.871 Hom.: 7222

Bravo AF: 0.835

Asia WGS AF: 0.933 AC: 3246 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.16
DANN	Benign	0.71

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: rs4700966; hg19: chr5-180065103;