rs6879285

chr5-180605885-A-Gchr5-180605885-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_182925.5(FLT4):c.3894-2495T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.385 in 152,066 control chromosomes in the GnomAD database, including 11,959 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.38 (11959 hom., cov: 33)
• Consequence: FLT4 NM_182925.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.292

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.561 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FLT4	NM_182925.5	c.3894-2495T>C		intron_variant		ENST00000261937.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FLT4	ENST00000261937.11	c.3894-2495T>C		intron_variant		1	NM_182925.5	P1
FLT4	ENST00000502603.5	n.594-2495T>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.385 AC: 58473 AN: 151948 Hom.: 11943 Cov.: 33

Gnomad AFR AF: 0.513

Gnomad AMI AF: 0.214

Gnomad AMR AF: 0.302

Gnomad ASJ AF: 0.418

Gnomad EAS AF: 0.577

Gnomad SAS AF: 0.392

Gnomad FIN AF: 0.282

Gnomad MID AF: 0.415

Gnomad NFE AF: 0.327

Gnomad OTH AF: 0.380

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

GnomAD4 genome AF: 0.385 AC: 58529 AN: 152066 Hom.: 11959 Cov.: 33 AF XY: 0.383 AC XY: 28497 AN XY: 74328

Gnomad4 AFR AF: 0.513

Gnomad4 AMR AF: 0.302

Gnomad4 ASJ AF: 0.418

Gnomad4 EAS AF: 0.578

Gnomad4 SAS AF: 0.391

Gnomad4 FIN AF: 0.282

Gnomad4 NFE AF: 0.327

Gnomad4 OTH AF: 0.386

Alfa AF: 0.352 Hom.: 2005

Bravo AF: 0.395

Asia WGS AF: 0.480 AC: 1672 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	1.1
Dann	Benign	0.38

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: rs6879285; hg19: chr5-180032885;