Variant 5-180621056-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_StrongBA1

The NM_182925.5(FLT4):c.2168-49G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.233 in 1,611,708 control chromosomes in the GnomAD database, including 45,077 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.24 ( 4445 hom., cov: 34)

Exomes 𝑓: 0.23 ( 40632 hom. )

Consequence

FLT4
NM_182925.5 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.11

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.96).

BP6

Variant 5-180621056-C-T is Benign according to our data. Variant chr5-180621056-C-T is described in ClinVar as [Benign]. Clinvar id is 263034.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.272 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FLT4	NM_182925.5 linkuse as main transcript	c.2168-49G>A		intron_variant		ENST00000261937.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FLT4	ENST00000261937.11 linkuse as main transcript	c.2168-49G>A		intron_variant		1	NM_182925.5	P1	P35916-2

Frequencies

GnomAD3 genomes

AF:

0.237

AC:

36057

AN:

152058

Hom.:

4441

Cov.:

show subpopulations

Gnomad AFR

AF:

0.259

Gnomad AMI

AF:

0.216

Gnomad AMR

AF:

0.191

Gnomad ASJ

AF:

0.300

Gnomad EAS

AF:

0.251

Gnomad SAS

AF:

0.287

Gnomad FIN

AF:

0.171

Gnomad MID

AF:

0.323

Gnomad NFE

AF:

0.237

Gnomad OTH

AF:

0.236

GnomAD3 exomes

AF:

0.231

AC:

56869

AN:

246522

Hom.:

6957

AF XY:

0.238

AC XY:

31950

AN XY:

134330

show subpopulations

Gnomad AFR exome

AF:

0.258

Gnomad AMR exome

AF:

0.148

Gnomad ASJ exome

AF:

0.296

Gnomad EAS exome

AF:

0.248

Gnomad SAS exome

AF:

0.298

Gnomad FIN exome

AF:

0.169

Gnomad NFE exome

AF:

0.236

Gnomad OTH exome

AF:

0.247

GnomAD4 exome

AF:

0.233

AC:

339900

AN:

1459530

Hom.:

40632

Cov.:

AF XY:

0.236

AC XY:

171013

AN XY:

725940

show subpopulations

Gnomad4 AFR exome

AF:

0.265

Gnomad4 AMR exome

AF:

0.152

Gnomad4 ASJ exome

AF:

0.292

Gnomad4 EAS exome

AF:

0.248

Gnomad4 SAS exome

AF:

0.294

Gnomad4 FIN exome

AF:

0.170

Gnomad4 NFE exome

AF:

0.230

Gnomad4 OTH exome

AF:

0.242

GnomAD4 genome

AF:

0.237

AC:

36084

AN:

152178

Hom.:

4445

Cov.:

AF XY:

0.236

AC XY:

17570

AN XY:

74392

show subpopulations

Gnomad4 AFR

AF:

0.260

Gnomad4 AMR

AF:

0.190

Gnomad4 ASJ

AF:

0.300

Gnomad4 EAS

AF:

0.252

Gnomad4 SAS

AF:

0.285

Gnomad4 FIN

AF:

0.171

Gnomad4 NFE

AF:

0.237

Gnomad4 OTH

AF:

0.234

Alfa

AF:

0.188

Hom.:

654

Bravo

AF:

0.239

Asia WGS

AF:

0.250

AC:

873

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Congenital heart defects, multiple types, 7

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 10, 2021

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 11, 2018

- -

Hereditary lymphedema type I

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.96

CADD

Benign

1.5

DANN

Benign

0.51

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.10

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