Genetic Variant FLT4:c.2761+44G>A (chr5-180619209-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

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

The NM_182925.5(FLT4):c.2761+44G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.686 in 1,433,730 control chromosomes in the GnomAD database, including 339,176 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.66 ( 33116 hom., cov: 33)

Exomes 𝑓: 0.69 ( 306060 hom. )

Consequence

FLT4
NM_182925.5 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.99

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=-0.82).

BP6

Variant 5-180619209-C-T is Benign according to our data. Variant chr5-180619209-C-T is described in ClinVar as [Benign]. Clinvar id is 263040.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.717 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FLT4	NM_182925.5 link	c.2761+44G>A		intron_variant	Intron 19 of 29	ENST00000261937.11	NP_891555.2	P35916-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FLT4	ENST00000261937.11 link	c.2761+44G>A		intron_variant	Intron 19 of 29	1	NM_182925.5	ENSP00000261937.6		P35916-2

Frequencies

GnomAD3 genomes

AF:

0.660

AC:

99091

AN:

150196

Hom.:

33088

Cov.:

show subpopulations

Gnomad AFR

AF:

0.600

Gnomad AMI

AF:

0.734

Gnomad AMR

AF:

0.728

Gnomad ASJ

AF:

0.652

Gnomad EAS

AF:

0.504

Gnomad SAS

AF:

0.650

Gnomad FIN

AF:

0.727

Gnomad MID

AF:

0.647

Gnomad NFE

AF:

0.682

Gnomad OTH

AF:

0.672

GnomAD3 exomes

AF:

0.712

AC:

91712

AN:

128860

Hom.:

32761

AF XY:

0.705

AC XY:

52139

AN XY:

73972

show subpopulations

Gnomad AFR exome

AF:

0.645

Gnomad AMR exome

AF:

0.817

Gnomad ASJ exome

AF:

0.696

Gnomad EAS exome

AF:

0.555

Gnomad SAS exome

AF:

0.672

Gnomad FIN exome

AF:

0.746

Gnomad NFE exome

AF:

0.711

Gnomad OTH exome

AF:

0.707

GnomAD4 exome

AF:

0.689

AC:

884712

AN:

1283426

Hom.:

306060

Cov.:

AF XY:

0.688

AC XY:

435977

AN XY:

633262

show subpopulations

Gnomad4 AFR exome

AF:

0.603

Gnomad4 AMR exome

AF:

0.802

Gnomad4 ASJ exome

AF:

0.684

Gnomad4 EAS exome

AF:

0.508

Gnomad4 SAS exome

AF:

0.662

Gnomad4 FIN exome

AF:

0.736

Gnomad4 NFE exome

AF:

0.694

Gnomad4 OTH exome

AF:

0.683

GnomAD4 genome

AF:

0.660

AC:

99163

AN:

150304

Hom.:

33116

Cov.:

AF XY:

0.661

AC XY:

48568

AN XY:

73442

show subpopulations

Gnomad4 AFR

AF:

0.600

Gnomad4 AMR

AF:

0.728

Gnomad4 ASJ

AF:

0.652

Gnomad4 EAS

AF:

0.503

Gnomad4 SAS

AF:

0.651

Gnomad4 FIN

AF:

0.727

Gnomad4 NFE

AF:

0.682

Gnomad4 OTH

AF:

0.668

Alfa

AF:

0.617

Hom.:

3383

Bravo

AF:

0.655

Asia WGS

AF:

0.598

AC:

2065

AN:

3454

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Congenital heart defects, multiple types, 7

Benign:1

Aug 10, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:1

Nov 11, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Hereditary lymphedema type I

Benign:1

Aug 10, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.21

DANN

Benign

0.81

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