rs13359473

Variant names:

• chr5-180629044-G-A
• rs13359473
• NM_182925.5:c.986-45C>T

Your query was ambiguous. Multiple possible variants found:

• chr5-180629044-G-A
• chr5-180629044-G-C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_182925.5(FLT4):​c.986-45C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.322 in 1,543,294 control chromosomes in the GnomAD database, including 83,165 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.28 (6467 hom., cov: 33)
  • Exomes 𝑓: 0.33 (76698 hom.)
• Consequence: FLT4 NM_182925.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.831
• Publications: 9 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP6: Variant 5-180629044-G-A is Benign according to our data. Variant chr5-180629044-G-A is described in ClinVar as [Benign]. Clinvar id is 263072.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.342 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FLT4	NM_182925.5	c.986-45C>T		intron_variant	Intron 7 of 29	ENST00000261937.11	NP_891555.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FLT4	ENST00000261937.11	c.986-45C>T		intron_variant	Intron 7 of 29	1	NM_182925.5	ENSP00000261937.6

Frequencies

GnomAD3 genomes AF: 0.275 AC: 41883 AN: 152064 Hom.: 6467 Cov.: 33

Gnomad AFR AF: 0.165

Gnomad AMI AF: 0.335

Gnomad AMR AF: 0.263

Gnomad ASJ AF: 0.302

Gnomad EAS AF: 0.0640

Gnomad SAS AF: 0.357

Gnomad FIN AF: 0.342

Gnomad MID AF: 0.385

Gnomad NFE AF: 0.343

Gnomad OTH AF: 0.285

GnomAD2 exomes AF: 0.295 AC: 73033 AN: 247560 AF XY: 0.308

Gnomad AFR exome AF: 0.161

Gnomad AMR exome AF: 0.216

Gnomad ASJ exome AF: 0.300

Gnomad EAS exome AF: 0.0542

Gnomad FIN exome AF: 0.348

Gnomad NFE exome AF: 0.344

Gnomad OTH exome AF: 0.323

GnomAD4 exome AF: 0.327 AC: 454749 AN: 1391112 Hom.: 76698 Cov.: 25 AF XY: 0.330 AC XY: 229948 AN XY: 695876

African (AFR) AF: 0.161 AC: 5151 AN: 32062

American (AMR) AF: 0.218 AC: 9733 AN: 44642

Ashkenazi Jewish (ASJ) AF: 0.301 AC: 7726 AN: 25662

East Asian (EAS) AF: 0.0790 AC: 3104 AN: 39310

South Asian (SAS) AF: 0.379 AC: 32194 AN: 84838

European-Finnish (FIN) AF: 0.352 AC: 18227 AN: 51834

Middle Eastern (MID) AF: 0.354 AC: 2000 AN: 5648

European-Non Finnish (NFE) AF: 0.341 AC: 358213 AN: 1049096

Other (OTH) AF: 0.317 AC: 18401 AN: 58020

GnomAD4 genome AF: 0.275 AC: 41882 AN: 152182 Hom.: 6467 Cov.: 33 AF XY: 0.279 AC XY: 20740 AN XY: 74418

African (AFR) AF: 0.165 AC: 6846 AN: 41544

American (AMR) AF: 0.262 AC: 4015 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.302 AC: 1049 AN: 3470

East Asian (EAS) AF: 0.0640 AC: 330 AN: 5160

South Asian (SAS) AF: 0.356 AC: 1717 AN: 4828

European-Finnish (FIN) AF: 0.342 AC: 3622 AN: 10596

Middle Eastern (MID) AF: 0.401 AC: 117 AN: 292

European-Non Finnish (NFE) AF: 0.343 AC: 23286 AN: 67974

Other (OTH) AF: 0.282 AC: 596 AN: 2114

Alfa AF: 0.245 Hom.: 939

Bravo AF: 0.258

Asia WGS AF: 0.203 AC: 709 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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	-0.94
CADD	Benign	4.9
DANN	Benign	0.39
PhyloP100		-0.83
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs13359473; hg19: chr5-180056044; COSMIC: COSV56102210; COSMIC: COSV56102210;