Genetic Variant FLT4:c.401-19G>C (chr5-180630356-C-G) – 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.401-19G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.102 in 1,601,888 control chromosomes in the GnomAD database, including 13,304 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.11 ( 1527 hom., cov: 32)

Exomes 𝑓: 0.10 ( 11777 hom. )

Consequence

FLT4
NM_182925.5 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.0790

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=-0.85).

BP6

Variant 5-180630356-C-G is Benign according to our data. Variant chr5-180630356-C-G is described in ClinVar as [Benign]. Clinvar id is 263060.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-180630356-C-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.515 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FLT4	NM_182925.5 link	c.401-19G>C		intron_variant	Intron 3 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.401-19G>C		intron_variant	Intron 3 of 29	1	NM_182925.5	ENSP00000261937.6		P35916-2

Frequencies

GnomAD3 genomes

AF:

0.113

AC:

17120

AN:

152016

Hom.:

1520

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0919

Gnomad AMI

AF:

0.00881

Gnomad AMR

AF:

0.0811

Gnomad ASJ

AF:

0.170

Gnomad EAS

AF:

0.531

Gnomad SAS

AF:

0.0873

Gnomad FIN

AF:

0.183

Gnomad MID

AF:

0.0637

Gnomad NFE

AF:

0.0904

Gnomad OTH

AF:

0.104

GnomAD3 exomes

AF:

0.131

AC:

31944

AN:

243052

Hom.:

4007

AF XY:

0.127

AC XY:

16810

AN XY:

132438

show subpopulations

Gnomad AFR exome

AF:

0.0982

Gnomad AMR exome

AF:

0.0880

Gnomad ASJ exome

AF:

0.173

Gnomad EAS exome

AF:

0.559

Gnomad SAS exome

AF:

0.0811

Gnomad FIN exome

AF:

0.172

Gnomad NFE exome

AF:

0.0852

Gnomad OTH exome

AF:

0.111

GnomAD4 exome

AF:

0.101

AC:

146580

AN:

1449752

Hom.:

11777

Cov.:

AF XY:

0.101

AC XY:

72671

AN XY:

721684

show subpopulations

Gnomad4 AFR exome

AF:

0.0936

Gnomad4 AMR exome

AF:

0.0857

Gnomad4 ASJ exome

AF:

0.166

Gnomad4 EAS exome

AF:

0.528

Gnomad4 SAS exome

AF:

0.0808

Gnomad4 FIN exome

AF:

0.161

Gnomad4 NFE exome

AF:

0.0837

Gnomad4 OTH exome

AF:

0.115

GnomAD4 genome

AF:

0.113

AC:

17152

AN:

152136

Hom.:

1527

Cov.:

AF XY:

0.117

AC XY:

8688

AN XY:

74358

show subpopulations

Gnomad4 AFR

AF:

0.0921

Gnomad4 AMR

AF:

0.0811

Gnomad4 ASJ

AF:

0.170

Gnomad4 EAS

AF:

0.532

Gnomad4 SAS

AF:

0.0880

Gnomad4 FIN

AF:

0.183

Gnomad4 NFE

AF:

0.0904

Gnomad4 OTH

AF:

0.112

Alfa

AF:

0.0812

Hom.:

136

Bravo

AF:

0.109

Asia WGS

AF:

0.282

AC:

981

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

PreventionGenetics, part of Exact Sciences

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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

1.9

DANN

Benign

0.37

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