Variant rs438464 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+18C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.5 in 1,545,306 control chromosomes in the GnomAD database, including 194,988 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.48 ( 17641 hom., cov: 31)

Exomes 𝑓: 0.50 ( 177347 hom. )

Consequence

FLT4
NM_182925.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.456

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 5-180628864-G-A is Benign according to our data. Variant chr5-180628864-G-A is described in ClinVar as [Benign]. Clinvar id is 263016.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-180628864-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.534 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FLT4	NM_182925.5 link	c.1103+18C>T		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.1103+18C>T		intron_variant		1	NM_182925.5	ENSP00000261937.6		P35916-2

Frequencies

GnomAD3 genomes

AF:

0.481

AC:

72806

AN:

151478

Hom.:

17637

Cov.:

show subpopulations

Gnomad AFR

AF:

0.443

Gnomad AMI

AF:

0.609

Gnomad AMR

AF:

0.544

Gnomad ASJ

AF:

0.466

Gnomad EAS

AF:

0.327

Gnomad SAS

AF:

0.453

Gnomad FIN

AF:

0.446

Gnomad MID

AF:

0.442

Gnomad NFE

AF:

0.507

Gnomad OTH

AF:

0.503

GnomAD3 exomes

AF:

0.471

AC:

107476

AN:

228020

Hom.:

24996

AF XY:

0.468

AC XY:

58564

AN XY:

125252

show subpopulations

Gnomad AFR exome

AF:

0.429

Gnomad AMR exome

AF:

0.562

Gnomad ASJ exome

AF:

0.451

Gnomad EAS exome

AF:

0.303

Gnomad SAS exome

AF:

0.432

Gnomad FIN exome

AF:

0.433

Gnomad NFE exome

AF:

0.495

Gnomad OTH exome

AF:

0.482

GnomAD4 exome

AF:

0.502

AC:

700164

AN:

1393714

Hom.:

177347

Cov.:

AF XY:

0.499

AC XY:

347295

AN XY:

695854

show subpopulations

Gnomad4 AFR exome

AF:

0.438

Gnomad4 AMR exome

AF:

0.568

Gnomad4 ASJ exome

AF:

0.462

Gnomad4 EAS exome

AF:

0.335

Gnomad4 SAS exome

AF:

0.435

Gnomad4 FIN exome

AF:

0.453

Gnomad4 NFE exome

AF:

0.517

Gnomad4 OTH exome

AF:

0.487

GnomAD4 genome

AF:

0.480

AC:

72836

AN:

151592

Hom.:

17641

Cov.:

AF XY:

0.475

AC XY:

35167

AN XY:

74056

show subpopulations

Gnomad4 AFR

AF:

0.443

Gnomad4 AMR

AF:

0.543

Gnomad4 ASJ

AF:

0.466

Gnomad4 EAS

AF:

0.326

Gnomad4 SAS

AF:

0.453

Gnomad4 FIN

AF:

0.446

Gnomad4 NFE

AF:

0.507

Gnomad4 OTH

AF:

0.498

Alfa

AF:

0.478

Hom.:

3188

Bravo

AF:

0.489

ClinVar

Significance: Benign

Submissions summary: Benign:4

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

- -

Congenital heart defects, multiple types, 7

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 10, 2021

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 11, 2018

- -

Hereditary lymphedema type I

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

DANN

Benign

0.70

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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