5-180605684-C-G

Position:

• chr5-180605684-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.3894-2294G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0384 in 152,304 control chromosomes in the GnomAD database, including 186 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 0.038 (186 hom., cov: 33)
• Consequence: FLT4 NM_182925.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.243

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.116 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FLT4	NM_182925.5	c.3894-2294G>C		intron_variant		ENST00000261937.11	NP_891555.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FLT4	ENST00000261937.11	c.3894-2294G>C		intron_variant		1	NM_182925.5	ENSP00000261937	P1
FLT4	ENST00000502603.5	n.594-2294G>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0385 AC: 5852 AN: 152186 Hom.: 185 Cov.: 33

Gnomad AFR AF: 0.00975

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0354

Gnomad ASJ AF: 0.0867

Gnomad EAS AF: 0.124

Gnomad SAS AF: 0.0315

Gnomad FIN AF: 0.0397

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0485

Gnomad OTH AF: 0.0363

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

GnomAD4 genome AF: 0.0384 AC: 5853 AN: 152304 Hom.: 186 Cov.: 33 AF XY: 0.0372 AC XY: 2773 AN XY: 74474

Gnomad4 AFR AF: 0.00969

Gnomad4 AMR AF: 0.0353

Gnomad4 ASJ AF: 0.0867

Gnomad4 EAS AF: 0.124

Gnomad4 SAS AF: 0.0317

Gnomad4 FIN AF: 0.0397

Gnomad4 NFE AF: 0.0485

Gnomad4 OTH AF: 0.0383

Alfa AF: 0.0376 Hom.: 14

Bravo AF: 0.0379

Asia WGS AF: 0.0740 AC: 260 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.5
DANN	Benign	0.66

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: rs17080412; hg19: chr5-180032684;