rs2290983

chr5-180631963-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_182925.5(FLT4):c.59-185C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.545 in 151,898 control chromosomes in the GnomAD database, including 23,110 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.54 (23110 hom., cov: 33)
• Consequence: FLT4 NM_182925.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.07

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 5-180631963-G-A is Benign according to our data. Variant chr5-180631963-G-A is described in ClinVar as [Benign]. Clinvar id is 1247443.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.601 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FLT4	NM_182925.5	c.59-185C>T		intron_variant		ENST00000261937.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FLT4	ENST00000261937.11	c.59-185C>T		intron_variant		1	NM_182925.5	P1

Frequencies

GnomAD3 genomes AF: 0.545 AC: 82684 AN: 151780 Hom.: 23099 Cov.: 33

Gnomad AFR AF: 0.421

Gnomad AMI AF: 0.355

Gnomad AMR AF: 0.612

Gnomad ASJ AF: 0.579

Gnomad EAS AF: 0.448

Gnomad SAS AF: 0.563

Gnomad FIN AF: 0.612

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.601

Gnomad OTH AF: 0.562

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

GnomAD4 genome AF: 0.545 AC: 82728 AN: 151898 Hom.: 23110 Cov.: 33 AF XY: 0.542 AC XY: 40268 AN XY: 74248

Gnomad4 AFR AF: 0.421

Gnomad4 AMR AF: 0.612

Gnomad4 ASJ AF: 0.579

Gnomad4 EAS AF: 0.448

Gnomad4 SAS AF: 0.563

Gnomad4 FIN AF: 0.612

Gnomad4 NFE AF: 0.601

Gnomad4 OTH AF: 0.559

Alfa AF: 0.587 Hom.: 30623

Bravo AF: 0.536

Asia WGS AF: 0.530 AC: 1842 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 11, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	0.64
Dann	Benign	0.96

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: rs2290983; hg19: chr5-180058963; COSMIC: COSV56112690; COSMIC: COSV56112690;