5-180608792-C-T

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.3893+176G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.064 in 152,188 control chromosomes in the GnomAD database, including 399 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.064 (399 hom., cov: 33)
• Consequence: FLT4 NM_182925.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.170

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=-0.9).
• BP6: Variant 5-180608792-C-T is Benign according to our data. Variant chr5-180608792-C-T is described in ClinVar as [Benign]. Clinvar id is 1268187.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0869 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FLT4	NM_182925.5	c.3893+176G>A		intron_variant		ENST00000261937.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FLT4	ENST00000261937.11	c.3893+176G>A		intron_variant		1	NM_182925.5	P1

Frequencies

GnomAD3 genomes AF: 0.0640 AC: 9736 AN: 152070 Hom.: 399 Cov.: 33

Gnomad AFR AF: 0.0254

Gnomad AMI AF: 0.268

Gnomad AMR AF: 0.0525

Gnomad ASJ AF: 0.109

Gnomad EAS AF: 0.000772

Gnomad SAS AF: 0.0394

Gnomad FIN AF: 0.0824

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0888

Gnomad OTH AF: 0.0641

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

GnomAD4 genome AF: 0.0640 AC: 9736 AN: 152188 Hom.: 399 Cov.: 33 AF XY: 0.0634 AC XY: 4719 AN XY: 74406

Gnomad4 AFR AF: 0.0253

Gnomad4 AMR AF: 0.0523

Gnomad4 ASJ AF: 0.109

Gnomad4 EAS AF: 0.000773

Gnomad4 SAS AF: 0.0394

Gnomad4 FIN AF: 0.0824

Gnomad4 NFE AF: 0.0888

Gnomad4 OTH AF: 0.0634

Alfa AF: 0.0674 Hom.: 49

Bravo AF: 0.0609

Asia WGS AF: 0.0260 AC: 89 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 19, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	3.7
Dann	Benign	0.81

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: rs307832; hg19: chr5-180035792; COSMIC: COSV56111021; COSMIC: COSV56111021;