rs2290983

Variant names:

• chr5-180631963-G-A
• rs2290983
• NM_182925.5:c.59-185C>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.59-185C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.545 in 151,898 control chromosomes in the GnomAD database, including 23,110 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.54 (23110 hom., cov: 33)
• Consequence: FLT4 NM_182925.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.07
• Publications: 7 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):

• 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 5-180631963-G-A is Benign according to our data. Variant chr5-180631963-G-A is described in ClinVar as Benign. ClinVar VariationId is 1247443.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.601 is higher than 0.05.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FLT4	NM_182925.5	MANE Select	c.59-185C>T		intron	N/A	NP_891555.2	P35916-2
	FLT4	NM_001354989.2		c.59-185C>T		intron	N/A	NP_001341918.1	E9PD35
	FLT4	NM_002020.5		c.59-185C>T		intron	N/A	NP_002011.2	P35916-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FLT4	ENST00000261937.11	TSL:1 MANE Select	c.59-185C>T		intron	N/A	ENSP00000261937.6	P35916-2
	FLT4	ENST00000502649.5	TSL:1	c.59-185C>T		intron	N/A	ENSP00000426057.1	E9PD35
	FLT4	ENST00000393347.7	TSL:1	c.59-185C>T		intron	N/A	ENSP00000377016.3	P35916-1

Frequencies

GnomAD3 genomes AF: 0.545 AC: 82684 AN: 151780 Hom.: 23099 Cov.: 33

Gnomad AFR AF: 0.421

Gnomad AMI AF: 0.355

Gnomad AMR AF: 0.612

Gnomad ASJ AF: 0.579

Gnomad EAS AF: 0.448

Gnomad SAS AF: 0.563

Gnomad FIN AF: 0.612

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.601

Gnomad OTH AF: 0.562

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.545 AC: 82728 AN: 151898 Hom.: 23110 Cov.: 33 AF XY: 0.542 AC XY: 40268 AN XY: 74248

African (AFR) AF: 0.421 AC: 17422 AN: 41394

American (AMR) AF: 0.612 AC: 9344 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.579 AC: 2010 AN: 3472

East Asian (EAS) AF: 0.448 AC: 2301 AN: 5140

South Asian (SAS) AF: 0.563 AC: 2716 AN: 4822

European-Finnish (FIN) AF: 0.612 AC: 6465 AN: 10570

Middle Eastern (MID) AF: 0.520 AC: 153 AN: 294

European-Non Finnish (NFE) AF: 0.601 AC: 40818 AN: 67918

Other (OTH) AF: 0.559 AC: 1177 AN: 2106

Alfa AF: 0.582 Hom.: 38262

Bravo AF: 0.536

Asia WGS AF: 0.530 AC: 1842 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.64
DANN	Benign	0.96
PhyloP100		-3.1
Mutation Taster		=100/0	polymorphism (auto)

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: rs2290983; hg19: chr5-180058963; COSMIC: COSV56112690; COSMIC: COSV56112690;