rs201306288

Positions:

• chr5-180625832-G-A

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
FLT4	NM_182925.5	c.1421+37C>T		intron_variant		ENST00000261937.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FLT4	ENST00000261937.11	c.1421+37C>T		intron_variant		1	NM_182925.5	P1

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

GnomAD3 exomes AF: 0.00275 AC: 655 AN: 238536 Hom.: 12 AF XY: 0.00207 AC XY: 269 AN XY: 130256

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 SAS exome AF: 0.0000664

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

Gnomad4 AFR exome AF: 0.0563

Gnomad4 AMR exome AF: 0.00203

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000369

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000417

Gnomad4 OTH exome AF: 0.00217

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

Gnomad4 AFR AF: 0.0533

Gnomad4 AMR AF: 0.00580

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000312

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000904

Gnomad4 OTH AF: 0.00958

Alfa AF: 0.0100 Hom.: 6

Bravo AF: 0.0129

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.7
DANN	Benign	0.53

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

LitVar

Other links and lift over

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