5-180603322-C-T

Variant names:

Variant summary

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

The NM_182925.5(FLT4):c.3962G>A(p.Arg1321Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0141 in 1,612,680 control chromosomes in the GnomAD database, including 192 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0093 ( 14 hom., cov: 33)

Exomes 𝑓: 0.015 ( 178 hom. )

Consequence

FLT4
NM_182925.5 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.776

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 (MetaRNN=0.0055611134).

BP6

Variant 5-180603322-C-T is Benign according to our data. Variant chr5-180603322-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 263055.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-180603322-C-T is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00927 (1412/152360) while in subpopulation NFE AF= 0.0163 (1108/68020). AF 95% confidence interval is 0.0155. There are 14 homozygotes in gnomad4. There are 639 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 14 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FLT4	NM_182925.5 link	c.3962G>A	p.Arg1321Gln	missense_variant	Exon 30 of 30	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.3962G>A	p.Arg1321Gln	missense_variant	Exon 30 of 30	1	NM_182925.5	ENSP00000261937.6		P35916-2
FLT4	ENST00000502603.5 link	n.662G>A		non_coding_transcript_exon_variant	Exon 4 of 4	2

Frequencies

GnomAD3 genomes

AF:

0.00929

AC:

1414

AN:

152242

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00282

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00556

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00414

Gnomad FIN

AF:

0.00602

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0163

Gnomad OTH

AF:

0.00718

GnomAD3 exomes

AF:

0.00891

AC:

2201

AN:

247058

Hom.:

AF XY:

0.00876

AC XY:

1175

AN XY:

134092

show subpopulations

Gnomad AFR exome

AF:

0.00233

Gnomad AMR exome

AF:

0.00587

Gnomad ASJ exome

AF:

0.000698

Gnomad EAS exome

AF:

0.0000546

Gnomad SAS exome

AF:

0.00279

Gnomad FIN exome

AF:

0.00777

Gnomad NFE exome

AF:

0.0149

Gnomad OTH exome

AF:

0.00990

GnomAD4 exome

AF:

0.0146

AC:

21327

AN:

1460320

Hom.:

178

Cov.:

AF XY:

0.0142

AC XY:

10333

AN XY:

726496

show subpopulations

Gnomad4 AFR exome

AF:

0.00203

Gnomad4 AMR exome

AF:

0.00604

Gnomad4 ASJ exome

AF:

0.000842

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00287

Gnomad4 FIN exome

AF:

0.00852

Gnomad4 NFE exome

AF:

0.0176

Gnomad4 OTH exome

AF:

0.0113

GnomAD4 genome

AF:

0.00927

AC:

1412

AN:

152360

Hom.:

Cov.:

AF XY:

0.00858

AC XY:

639

AN XY:

74500

show subpopulations

Gnomad4 AFR

AF:

0.00281

Gnomad4 AMR

AF:

0.00555

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00393

Gnomad4 FIN

AF:

0.00602

Gnomad4 NFE

AF:

0.0163

Gnomad4 OTH

AF:

0.00710

Alfa

AF:

0.0129

Hom.:

Bravo

AF:

0.00920

TwinsUK

AF:

0.0191

AC:

ALSPAC

AF:

0.0192

AC:

ESP6500AA

AF:

0.00295

AC:

ESP6500EA

AF:

0.0164

AC:

141

ExAC

AF:

0.00956

AC:

1160

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

Sep 20, 2023

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.076

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.52

CADD

Benign

7.1

DANN

Benign

0.96

DEOGEN2

Benign

0.086

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.072

LIST_S2

Benign

0.71

MetaRNN

Benign

0.0056

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

PrimateAI

Benign

0.26

PROVEAN

Benign

-0.36

REVEL

Benign

0.080

Sift

Benign

0.19

Sift4G

Benign

0.63

Polyphen

0.0010

Vest4

0.11

MVP

0.093

MPC

0.13

ClinPred

0.0062

GERP RS

1.4

Varity_R

0.027

gMVP

0.25

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