Variant 5-180630371-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_182925.5(FLT4):c.401-34G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0163 in 1,590,652 control chromosomes in the GnomAD database, including 272 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.013 ( 21 hom., cov: 32)

Exomes 𝑓: 0.017 ( 251 hom. )

Consequence

FLT4
NM_182925.5 intron

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -2.91

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=-0.89).

BP6

Variant 5-180630371-C-T is Benign according to our data. Variant chr5-180630371-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 263061.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0126 (1912/152206) while in subpopulation NFE AF= 0.0184 (1250/67994). AF 95% confidence interval is 0.0175. There are 21 homozygotes in gnomad4. There are 946 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 21 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FLT4	NM_182925.5 linkuse as main transcript	c.401-34G>A		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.401-34G>A		intron_variant		1	NM_182925.5	ENSP00000261937	P1	P35916-2

Frequencies

GnomAD3 genomes

AF:

0.0126

AC:

1912

AN:

152088

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00343

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0158

Gnomad ASJ

AF:

0.0283

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00477

Gnomad FIN

AF:

0.0107

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.0184

Gnomad OTH

AF:

0.0182

GnomAD3 exomes

AF:

0.0127

AC:

3045

AN:

239934

Hom.:

AF XY:

0.0128

AC XY:

1672

AN XY:

130954

show subpopulations

Gnomad AFR exome

AF:

0.00299

Gnomad AMR exome

AF:

0.00735

Gnomad ASJ exome

AF:

0.0270

Gnomad EAS exome

AF:

0.000110

Gnomad SAS exome

AF:

0.00463

Gnomad FIN exome

AF:

0.0113

Gnomad NFE exome

AF:

0.0187

Gnomad OTH exome

AF:

0.0156

GnomAD4 exome

AF:

0.0167

AC:

23982

AN:

1438446

Hom.:

251

Cov.:

AF XY:

0.0163

AC XY:

11711

AN XY:

716556

show subpopulations

Gnomad4 AFR exome

AF:

0.00292

Gnomad4 AMR exome

AF:

0.00757

Gnomad4 ASJ exome

AF:

0.0287

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.00504

Gnomad4 FIN exome

AF:

0.0100

Gnomad4 NFE exome

AF:

0.0189

Gnomad4 OTH exome

AF:

0.0170

GnomAD4 genome

AF:

0.0126

AC:

1912

AN:

152206

Hom.:

Cov.:

AF XY:

0.0127

AC XY:

946

AN XY:

74410

show subpopulations

Gnomad4 AFR

AF:

0.00342

Gnomad4 AMR

AF:

0.0158

Gnomad4 ASJ

AF:

0.0283

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00456

Gnomad4 FIN

AF:

0.0107

Gnomad4 NFE

AF:

0.0184

Gnomad4 OTH

AF:

0.0185

Alfa

AF:

0.0158

Hom.:

Bravo

AF:

0.0121

Asia WGS

AF:

0.00260

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

not provided

Benign:1

Likely benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.073

DANN

Benign

0.43

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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