5-180625832-G-A

Variant names:

• chr5-180625832-G-A
• rs201306288
• NM_182925.5:c.1421+37C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_182925.5(FLT4):​c.1421+37C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00225 in 1,514,824 control chromosomes in the GnomAD database, including 71 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 (34 hom., cov: 32)
  • Exomes 𝑓: 0.0012 (37 hom.)
• Consequence: FLT4 NM_182925.5 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.00
• Publications: 0 publications found

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):

• lymphatic malformation 1

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P
• capillary infantile hemangioma

  Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp
• congenital heart defects, multiple types, 7

  Inheritance: AD Classification: STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• lymphatic malformation

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• tetralogy of fallot

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 5-180625832-G-A is Benign according to our data. Variant chr5-180625832-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 263026.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0512 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FLT4	NM_182925.5	c.1421+37C>T		intron_variant	Intron 10 of 29	ENST00000261937.11	NP_891555.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FLT4	ENST00000261937.11	c.1421+37C>T		intron_variant	Intron 10 of 29	1	NM_182925.5	ENSP00000261937.6

Frequencies

GnomAD3 genomes AF: 0.0131 AC: 1770 AN: 135474 Hom.: 34 Cov.: 32

Gnomad AFR AF: 0.0533

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00580

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000311

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000904

Gnomad OTH AF: 0.00957

GnomAD2 exomes AF: 0.00275 AC: 655 AN: 238536 AF XY: 0.00207

Gnomad AFR exome AF: 0.0398

Gnomad AMR exome AF: 0.00127

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000753

Gnomad OTH exome AF: 0.000514

GnomAD4 exome AF: 0.00118 AC: 1633 AN: 1379316 Hom.: 37 Cov.: 29 AF XY: 0.00100 AC XY: 690 AN XY: 687096

African (AFR) AF: 0.0563 AC: 1380 AN: 24504

American (AMR) AF: 0.00203 AC: 80 AN: 39506

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23626

East Asian (EAS) AF: 0.00 AC: 0 AN: 25356

South Asian (SAS) AF: 0.0000369 AC: 3 AN: 81234

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48018

Middle Eastern (MID) AF: 0.00130 AC: 5 AN: 3844

European-Non Finnish (NFE) AF: 0.0000417 AC: 45 AN: 1077890

Other (OTH) AF: 0.00217 AC: 120 AN: 55338

GnomAD4 genome AF: 0.0131 AC: 1775 AN: 135508 Hom.: 34 Cov.: 32 AF XY: 0.0126 AC XY: 832 AN XY: 65994

African (AFR) AF: 0.0533 AC: 1668 AN: 31268

American (AMR) AF: 0.00580 AC: 82 AN: 14140

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3178

East Asian (EAS) AF: 0.000312 AC: 1 AN: 3202

South Asian (SAS) AF: 0.00 AC: 0 AN: 4508

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9766

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 264

European-Non Finnish (NFE) AF: 0.0000904 AC: 6 AN: 66392

Other (OTH) AF: 0.00958 AC: 18 AN: 1878

Alfa AF: 0.0230 Hom.: 10

Bravo AF: 0.0129

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

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
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.7
DANN	Benign	0.53
PhyloP100		0.0
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs201306288; hg19: chr5-180052832; COSMIC: COSV56104894;