rs2242216

Variant names:

• chr5-180614491-C-T
• rs2242216
• NM_182925.5:c.3220-312G>A

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.3220-312G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.379 in 151,926 control chromosomes in the GnomAD database, including 12,348 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.38 (12348 hom., cov: 31)
• Consequence: FLT4 NM_182925.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.11
• Publications: 4 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=-0.9).
• BP6: Variant 5-180614491-C-T is Benign according to our data. Variant chr5-180614491-C-T is described in ClinVar as [Benign]. Clinvar id is 1235762.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.472 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FLT4	NM_182925.5	c.3220-312G>A		intron_variant	Intron 23 of 29	ENST00000261937.11	NP_891555.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FLT4	ENST00000261937.11	c.3220-312G>A		intron_variant	Intron 23 of 29	1	NM_182925.5	ENSP00000261937.6

Frequencies

GnomAD3 genomes AF: 0.380 AC: 57636 AN: 151808 Hom.: 12354 Cov.: 31

Gnomad AFR AF: 0.168

Gnomad AMI AF: 0.416

Gnomad AMR AF: 0.421

Gnomad ASJ AF: 0.388

Gnomad EAS AF: 0.309

Gnomad SAS AF: 0.472

Gnomad FIN AF: 0.511

Gnomad MID AF: 0.399

Gnomad NFE AF: 0.476

Gnomad OTH AF: 0.398

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

GnomAD4 genome AF: 0.379 AC: 57642 AN: 151926 Hom.: 12348 Cov.: 31 AF XY: 0.383 AC XY: 28417 AN XY: 74240

African (AFR) AF: 0.168 AC: 6956 AN: 41454

American (AMR) AF: 0.422 AC: 6439 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.388 AC: 1347 AN: 3472

East Asian (EAS) AF: 0.308 AC: 1582 AN: 5136

South Asian (SAS) AF: 0.472 AC: 2274 AN: 4814

European-Finnish (FIN) AF: 0.511 AC: 5408 AN: 10582

Middle Eastern (MID) AF: 0.384 AC: 113 AN: 294

European-Non Finnish (NFE) AF: 0.476 AC: 32315 AN: 67878

Other (OTH) AF: 0.393 AC: 829 AN: 2108

Alfa AF: 0.428 Hom.: 3540

Bravo AF: 0.361

Asia WGS AF: 0.381 AC: 1325 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Nov 11, 2018

GeneDx

Significance: 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	-0.90
CADD	Benign	0.20
DANN	Benign	0.47
PhyloP100		-1.1
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: rs2242216; hg19: chr5-180041491;