Variant rs2242215 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.2168-28A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0634 in 1,610,814 control chromosomes in the GnomAD database, including 4,043 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.059 ( 330 hom., cov: 34)

Exomes 𝑓: 0.064 ( 3713 hom. )

Consequence

FLT4
NM_182925.5 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.443

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

This place is a probable branch point but likely benign (scored 1 / 10). Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 5-180621035-T-C is Benign according to our data. Variant chr5-180621035-T-C is described in ClinVar as [Benign]. Clinvar id is 263033.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.174 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FLT4	NM_182925.5 link	c.2168-28A>G		intron_variant		ENST00000261937.11	NP_891555.2	P35916-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FLT4	ENST00000261937.11 link	c.2168-28A>G		intron_variant		1	NM_182925.5	ENSP00000261937.6		P35916-2

Frequencies

GnomAD3 genomes

AF:

0.0586

AC:

8905

AN:

152028

Hom.:

327

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0457

Gnomad AMI

AF:

0.00768

Gnomad AMR

AF:

0.0382

Gnomad ASJ

AF:

0.117

Gnomad EAS

AF:

0.183

Gnomad SAS

AF:

0.136

Gnomad FIN

AF:

0.0381

Gnomad MID

AF:

0.0759

Gnomad NFE

AF:

0.0570

Gnomad OTH

AF:

0.0547

GnomAD3 exomes

AF:

0.0735

AC:

18119

AN:

246478

Hom.:

921

AF XY:

0.0778

AC XY:

10445

AN XY:

134306

show subpopulations

Gnomad AFR exome

AF:

0.0444

Gnomad AMR exome

AF:

0.0390

Gnomad ASJ exome

AF:

0.111

Gnomad EAS exome

AF:

0.185

Gnomad SAS exome

AF:

0.134

Gnomad FIN exome

AF:

0.0372

Gnomad NFE exome

AF:

0.0572

Gnomad OTH exome

AF:

0.0710

GnomAD4 exome

AF:

0.0639

AC:

93197

AN:

1458668

Hom.:

3713

Cov.:

AF XY:

0.0663

AC XY:

48074

AN XY:

725332

show subpopulations

Gnomad4 AFR exome

AF:

0.0471

Gnomad4 AMR exome

AF:

0.0407

Gnomad4 ASJ exome

AF:

0.110

Gnomad4 EAS exome

AF:

0.187

Gnomad4 SAS exome

AF:

0.132

Gnomad4 FIN exome

AF:

0.0369

Gnomad4 NFE exome

AF:

0.0554

Gnomad4 OTH exome

AF:

0.0703

GnomAD4 genome

AF:

0.0586

AC:

8914

AN:

152146

Hom.:

330

Cov.:

AF XY:

0.0591

AC XY:

4396

AN XY:

74380

show subpopulations

Gnomad4 AFR

AF:

0.0459

Gnomad4 AMR

AF:

0.0380

Gnomad4 ASJ

AF:

0.117

Gnomad4 EAS

AF:

0.184

Gnomad4 SAS

AF:

0.135

Gnomad4 FIN

AF:

0.0381

Gnomad4 NFE

AF:

0.0570

Gnomad4 OTH

AF:

0.0551

Alfa

AF:

0.0640

Hom.:

Bravo

AF:

0.0585

Asia WGS

AF:

0.133

AC:

465

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

4.9

DANN

Benign

0.32

La Branchor

0.71

BranchPoint Hunter

1.0

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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