rs201575824

chr5-180618739-A-Cchr5-180618739-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_182925.5(FLT4):c.3001+31T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00695 in 1,575,062 control chromosomes in the GnomAD database, including 44 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0045 (2 hom., cov: 33)
  • Exomes 𝑓: 0.0072 (42 hom.)
• Consequence: FLT4 NM_182925.5 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.65

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=-0.96).
• BP6: Variant 5-180618739-A-C is Benign according to our data. Variant chr5-180618739-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 263041.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00449 (684/152220) while in subpopulation NFE AF= 0.00754 (513/67996). AF 95% confidence interval is 0.007. There are 2 homozygotes in gnomad4. There are 315 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 2 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FLT4	NM_182925.5	c.3001+31T>G		intron_variant		ENST00000261937.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FLT4	ENST00000261937.11	c.3001+31T>G		intron_variant		1	NM_182925.5	P1

Frequencies

GnomAD3 genomes AF: 0.00450 AC: 684 AN: 152102 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.00159

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00262

Gnomad ASJ AF: 0.00288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00186

Gnomad FIN AF: 0.00359

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00754

Gnomad OTH AF: 0.00382

GnomAD3 exomes AF: 0.00424 AC: 777 AN: 183450 Hom.: 1 AF XY: 0.00439 AC XY: 438 AN XY: 99670

Gnomad AFR exome AF: 0.000477

Gnomad AMR exome AF: 0.00248

Gnomad ASJ exome AF: 0.00418

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00266

Gnomad FIN exome AF: 0.00421

Gnomad NFE exome AF: 0.00667

Gnomad OTH exome AF: 0.00495

GnomAD4 exome AF: 0.00722 AC: 10269 AN: 1422842 Hom.: 42 Cov.: 34 AF XY: 0.00718 AC XY: 5059 AN XY: 704684

Gnomad4 AFR exome AF: 0.000740

Gnomad4 AMR exome AF: 0.00244

Gnomad4 ASJ exome AF: 0.00463

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00287

Gnomad4 FIN exome AF: 0.00417

Gnomad4 NFE exome AF: 0.00843

Gnomad4 OTH exome AF: 0.00606

GnomAD4 genome AF: 0.00449 AC: 684 AN: 152220 Hom.: 2 Cov.: 33 AF XY: 0.00423 AC XY: 315 AN XY: 74420

Gnomad4 AFR AF: 0.00159

Gnomad4 AMR AF: 0.00262

Gnomad4 ASJ AF: 0.00288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00186

Gnomad4 FIN AF: 0.00359

Gnomad4 NFE AF: 0.00754

Gnomad4 OTH AF: 0.00378

Alfa AF: 0.00656 Hom.: 1

Bravo AF: 0.00435

Asia WGS AF: 0.00144 AC: 5 AN: 3478

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	-0.96
Cadd	Benign	0.54
Dann	Benign	0.43

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: rs201575824; hg19: chr5-180045739;