Variant rs383985 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.1103+20A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0782 in 1,537,158 control chromosomes in the GnomAD database, including 5,450 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.067 ( 482 hom., cov: 31)

Exomes 𝑓: 0.079 ( 4968 hom. )

Consequence

FLT4
NM_182925.5 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -4.07

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=-0.98).

BP6

Variant 5-180628862-T-C is Benign according to our data. Variant chr5-180628862-T-C is described in ClinVar as [Benign]. Clinvar id is 263018.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-180628862-T-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.114 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.1103+20A>G		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.1103+20A>G		intron_variant		1	NM_182925.5	ENSP00000261937	P1	P35916-2

Frequencies

GnomAD3 genomes

AF:

0.0675

AC:

10221

AN:

151418

Hom.:

482

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0166

Gnomad AMI

AF:

0.00881

Gnomad AMR

AF:

0.0472

Gnomad ASJ

AF:

0.141

Gnomad EAS

AF:

0.122

Gnomad SAS

AF:

0.0370

Gnomad FIN

AF:

0.140

Gnomad MID

AF:

0.0353

Gnomad NFE

AF:

0.0873

Gnomad OTH

AF:

0.0541

GnomAD3 exomes

AF:

0.0728

AC:

16453

AN:

226054

Hom.:

775

AF XY:

0.0729

AC XY:

9058

AN XY:

124270

show subpopulations

Gnomad AFR exome

AF:

0.0177

Gnomad AMR exome

AF:

0.0314

Gnomad ASJ exome

AF:

0.140

Gnomad EAS exome

AF:

0.122

Gnomad SAS exome

AF:

0.0400

Gnomad FIN exome

AF:

0.130

Gnomad NFE exome

AF:

0.0807

Gnomad OTH exome

AF:

0.0754

GnomAD4 exome

AF:

0.0793

AC:

109917

AN:

1385626

Hom.:

4968

Cov.:

AF XY:

0.0788

AC XY:

54509

AN XY:

692172

show subpopulations

Gnomad4 AFR exome

AF:

0.0143

Gnomad4 AMR exome

AF:

0.0338

Gnomad4 ASJ exome

AF:

0.135

Gnomad4 EAS exome

AF:

0.132

Gnomad4 SAS exome

AF:

0.0396

Gnomad4 FIN exome

AF:

0.124

Gnomad4 NFE exome

AF:

0.0814

Gnomad4 OTH exome

AF:

0.0781

GnomAD4 genome

AF:

0.0674

AC:

10219

AN:

151532

Hom.:

482

Cov.:

AF XY:

0.0680

AC XY:

5035

AN XY:

74024

show subpopulations

Gnomad4 AFR

AF:

0.0165

Gnomad4 AMR

AF:

0.0471

Gnomad4 ASJ

AF:

0.141

Gnomad4 EAS

AF:

0.122

Gnomad4 SAS

AF:

0.0374

Gnomad4 FIN

AF:

0.140

Gnomad4 NFE

AF:

0.0873

Gnomad4 OTH

AF:

0.0559

Alfa

AF:

0.0988

Hom.:

1932

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 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.98

CADD

Benign

0.51

DANN

Benign

0.10

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