rs2934601

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBP6_Very_Strong

The NM_182925.5(FLT4):c.3220-21A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. There is a variant allele frequency bias in the population database for this variant (GnomAd4), which may indicate mosaicism or somatic mutations in the reference population data. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.0022 ( 0 hom., cov: 0)

Exomes 𝑓: 0.0011 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

FLT4
NM_182925.5 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.575

Publications

1 publications found

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 Gene-Disease associations (from GenCC):

congenital heart defects, multiple types, 7
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, ClinGen, Labcorp Genetics (formerly Invitae)
lymphatic malformation 1
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, ClinGen, Ambry Genetics, Labcorp Genetics (formerly Invitae)
capillary infantile hemangioma
Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp
lymphatic malformation
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
tetralogy of fallot
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

FLT4 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

This position, referring to a specific DNA site, is a probable branch point but is likely benign (scored 1 / 10, using the threshold of <=3). The score ranges from 0 to 10, with values ≤3 considered benign and >5 classified as pathogenic. Computational evidence support a benign effect (BayesDel_noAF=-0.97).

BP6

Variant 5-180614200-T-G is Benign according to our data. Variant chr5-180614200-T-G is described in ClinVar as Likely_benign. ClinVar VariationId is 263048.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182925.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
FLT4	NM_182925.5	MANE Select	c.3220-21A>C	intron	N/A	NP_891555.2	P35916-2
FLT4	NM_001354989.2		c.3220-21A>C	intron	N/A	NP_001341918.1	E9PD35
FLT4	NM_002020.5		c.3220-21A>C	intron	N/A	NP_002011.2	P35916-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
FLT4	ENST00000261937.11	TSL:1 MANE Select	c.3220-21A>C	intron	N/A	ENSP00000261937.6	P35916-2
FLT4	ENST00000502649.5	TSL:1	c.3220-21A>C	intron	N/A	ENSP00000426057.1	E9PD35
FLT4	ENST00000393347.7	TSL:1	c.3220-21A>C	intron	N/A	ENSP00000377016.3	P35916-1

Frequencies

GnomAD3 genomes

AF:

0.00217

AC:

AN:

34140

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00416

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000412

Gnomad ASJ

AF:

0.00166

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00246

Gnomad FIN

AF:

0.00142

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000650

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00114

AC:

1060

AN:

929600

Hom.:

Cov.:

AF XY:

0.00108

AC XY:

498

AN XY:

459394

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00531

AC:

122

AN:

22990

American (AMR)

AF:

0.000438

AC:

AN:

29674

Ashkenazi Jewish (ASJ)

AF:

0.000711

AC:

AN:

14066

East Asian (EAS)

AF:

0.000356

AC:

AN:

19660

South Asian (SAS)

AF:

0.000869

AC:

AN:

43730

European-Finnish (FIN)

AF:

0.00

AC:

AN:

31596

Middle Eastern (MID)

AF:

0.00288

AC:

AN:

3820

European-Non Finnish (NFE)

AF:

0.00111

AC:

812

AN:

729796

Other (OTH)

AF:

0.00137

AC:

AN:

34268

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.280

Heterozygous variant carriers

137

274

412

549

686

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

138

184

230

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00222

AC:

AN:

34206

Hom.:

Cov.:

AF XY:

0.00252

AC XY:

AN XY:

16692

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00429

AC:

AN:

14468

American (AMR)

AF:

0.000411

AC:

AN:

2432

Ashkenazi Jewish (ASJ)

AF:

0.00166

AC:

AN:

604

East Asian (EAS)

AF:

0.00

AC:

AN:

1478

South Asian (SAS)

AF:

0.00246

AC:

AN:

814

European-Finnish (FIN)

AF:

0.00142

AC:

AN:

1404

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.000650

AC:

AN:

12312

Other (OTH)

AF:

0.00

AC:

AN:

472

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000000000000444089), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.366

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000762

Hom.:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.97

CADD

Benign

1.1

(source)

DANN

Benign

0.23

PhyloP100

-0.57

BranchPoint Hunter

1.0

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over