Variant rs56193546 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_182925.5(FLT4):c.1258+14G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0408 in 1,612,718 control chromosomes in the GnomAD database, including 1,999 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.044 ( 210 hom., cov: 33)

Exomes 𝑓: 0.040 ( 1789 hom. )

Consequence

FLT4
NM_182925.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.277

Variant links:

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]

FLT4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 5-180626097-C-T is Benign according to our data. Variant chr5-180626097-C-T is described in ClinVar as [Benign]. Clinvar id is 263021.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-180626097-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.173 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FLT4	NM_182925.5 linkuse as main transcript	c.1258+14G>A		intron_variant		ENST00000261937.11	NP_891555.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FLT4	ENST00000261937.11 linkuse as main transcript	c.1258+14G>A		intron_variant		1	NM_182925.5	ENSP00000261937	P1	P35916-2

Frequencies

GnomAD3 genomes

AF:

0.0443

AC:

6744

AN:

152120

Hom.:

208

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0516

Gnomad AMI

AF:

0.00439

Gnomad AMR

AF:

0.0302

Gnomad ASJ

AF:

0.0931

Gnomad EAS

AF:

0.183

Gnomad SAS

AF:

0.0891

Gnomad FIN

AF:

0.0220

Gnomad MID

AF:

0.0411

Gnomad NFE

AF:

0.0310

Gnomad OTH

AF:

0.0417

GnomAD3 exomes

AF:

0.0528

AC:

13138

AN:

249044

Hom.:

606

AF XY:

0.0541

AC XY:

7322

AN XY:

135288

show subpopulations

Gnomad AFR exome

AF:

0.0517

Gnomad AMR exome

AF:

0.0312

Gnomad ASJ exome

AF:

0.0918

Gnomad EAS exome

AF:

0.182

Gnomad SAS exome

AF:

0.0846

Gnomad FIN exome

AF:

0.0214

Gnomad NFE exome

AF:

0.0322

Gnomad OTH exome

AF:

0.0529

GnomAD4 exome

AF:

0.0404

AC:

59031

AN:

1460480

Hom.:

1789

Cov.:

AF XY:

0.0416

AC XY:

30191

AN XY:

726526

show subpopulations

Gnomad4 AFR exome

AF:

0.0504

Gnomad4 AMR exome

AF:

0.0320

Gnomad4 ASJ exome

AF:

0.0903

Gnomad4 EAS exome

AF:

0.178

Gnomad4 SAS exome

AF:

0.0829

Gnomad4 FIN exome

AF:

0.0229

Gnomad4 NFE exome

AF:

0.0314

Gnomad4 OTH exome

AF:

0.0494

GnomAD4 genome

AF:

0.0444

AC:

6753

AN:

152238

Hom.:

210

Cov.:

AF XY:

0.0449

AC XY:

3339

AN XY:

74434

show subpopulations

Gnomad4 AFR

AF:

0.0517

Gnomad4 AMR

AF:

0.0301

Gnomad4 ASJ

AF:

0.0931

Gnomad4 EAS

AF:

0.183

Gnomad4 SAS

AF:

0.0886

Gnomad4 FIN

AF:

0.0220

Gnomad4 NFE

AF:

0.0310

Gnomad4 OTH

AF:

0.0427

Alfa

AF:

0.0442

Hom.:

Bravo

AF:

0.0466

Asia WGS

AF:

0.113

AC:

391

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

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

2.8

DANN

Benign

0.53

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over