Variant 5-180649460-G-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.58+28C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00583 in 1,447,678 control chromosomes in the GnomAD database, including 336 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.027 ( 171 hom., cov: 33)

Exomes 𝑓: 0.0034 ( 165 hom. )

Consequence

FLT4
NM_182925.5 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.288

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:

FLT4 (HGNC:):

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=-0.76).

BP6

Variant 5-180649460-G-C is Benign according to our data. Variant chr5-180649460-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 263065.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0875 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.58+28C>G		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 linkuse as main transcript	c.58+28C>G		intron_variant		1	NM_182925.5	ENSP00000261937.6		P35916-2

Frequencies

GnomAD3 genomes

AF:

0.0266

AC:

4041

AN:

151752

Hom.:

170

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0898

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0106

Gnomad ASJ

AF:

0.0112

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00103

Gnomad FIN

AF:

0.0000957

Gnomad MID

AF:

0.0255

Gnomad NFE

AF:

0.00109

Gnomad OTH

AF:

0.0187

GnomAD3 exomes

AF:

0.00381

AC:

306

AN:

80248

Hom.:

AF XY:

0.00297

AC XY:

136

AN XY:

45808

show subpopulations

Gnomad AFR exome

AF:

0.0989

Gnomad AMR exome

AF:

0.00512

Gnomad ASJ exome

AF:

0.0107

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000705

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00127

Gnomad OTH exome

AF:

0.00470

GnomAD4 exome

AF:

0.00339

AC:

4387

AN:

1295818

Hom.:

165

Cov.:

AF XY:

0.00314

AC XY:

2006

AN XY:

639374

show subpopulations

Gnomad4 AFR exome

AF:

0.0975

Gnomad4 AMR exome

AF:

0.00692

Gnomad4 ASJ exome

AF:

0.0104

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000885

Gnomad4 FIN exome

AF:

0.000124

Gnomad4 NFE exome

AF:

0.000861

Gnomad4 OTH exome

AF:

0.00747

GnomAD4 genome

AF:

0.0267

AC:

4058

AN:

151860

Hom.:

171

Cov.:

AF XY:

0.0257

AC XY:

1911

AN XY:

74234

show subpopulations

Gnomad4 AFR

AF:

0.0899

Gnomad4 AMR

AF:

0.0106

Gnomad4 ASJ

AF:

0.0112

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.0000957

Gnomad4 NFE

AF:

0.00109

Gnomad4 OTH

AF:

0.0185

Alfa

AF:

0.0152

Hom.:

Bravo

AF:

0.0307

Asia WGS

AF:

0.00654

AC:

AN:

3378

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 11, 2018	- -

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

2.5

DANN

Benign

0.53

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