Variant chr5-180614208-T-C 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.3220-29A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.753 in 1,286,228 control chromosomes in the GnomAD database, including 360,821 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.76 ( 34377 hom., cov: 27)

Exomes 𝑓: 0.75 ( 326444 hom. )

Consequence

FLT4
NM_182925.5 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.96

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=-0.91).

BP6

Variant 5-180614208-T-C is Benign according to our data. Variant chr5-180614208-T-C is described in ClinVar as [Benign]. Clinvar id is 263049.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.81 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.3220-29A>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.3220-29A>G		intron_variant		1	NM_182925.5	ENSP00000261937	P1	P35916-2

Frequencies

GnomAD3 genomes

AF:

0.763

AC:

94348

AN:

123644

Hom.:

34362

Cov.:

show subpopulations

Gnomad AFR

AF:

0.692

Gnomad AMI

AF:

0.818

Gnomad AMR

AF:

0.823

Gnomad ASJ

AF:

0.771

Gnomad EAS

AF:

0.643

Gnomad SAS

AF:

0.764

Gnomad FIN

AF:

0.811

Gnomad MID

AF:

0.754

Gnomad NFE

AF:

0.794

Gnomad OTH

AF:

0.762

GnomAD3 exomes

AF:

0.723

AC:

152660

AN:

211094

Hom.:

56589

AF XY:

0.716

AC XY:

82829

AN XY:

115704

show subpopulations

Gnomad AFR exome

AF:

0.644

Gnomad AMR exome

AF:

0.808

Gnomad ASJ exome

AF:

0.693

Gnomad EAS exome

AF:

0.569

Gnomad SAS exome

AF:

0.665

Gnomad FIN exome

AF:

0.762

Gnomad NFE exome

AF:

0.743

Gnomad OTH exome

AF:

0.729

GnomAD4 exome

AF:

0.752

AC:

874231

AN:

1162452

Hom.:

326444

Cov.:

AF XY:

0.750

AC XY:

435759

AN XY:

580772

show subpopulations

Gnomad4 AFR exome

AF:

0.661

Gnomad4 AMR exome

AF:

0.804

Gnomad4 ASJ exome

AF:

0.717

Gnomad4 EAS exome

AF:

0.605

Gnomad4 SAS exome

AF:

0.709

Gnomad4 FIN exome

AF:

0.796

Gnomad4 NFE exome

AF:

0.761

Gnomad4 OTH exome

AF:

0.743

GnomAD4 genome

AF:

0.763

AC:

94418

AN:

123776

Hom.:

34377

Cov.:

AF XY:

0.763

AC XY:

46095

AN XY:

60390

show subpopulations

Gnomad4 AFR

AF:

0.692

Gnomad4 AMR

AF:

0.823

Gnomad4 ASJ

AF:

0.771

Gnomad4 EAS

AF:

0.642

Gnomad4 SAS

AF:

0.763

Gnomad4 FIN

AF:

0.811

Gnomad4 NFE

AF:

0.794

Gnomad4 OTH

AF:

0.757

Alfa

AF:

0.570

Hom.:

990

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

-0.91

CADD

Benign

0.040

DANN

Benign

0.33

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