rs56127961
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_182925.5(FLT4):c.3147C>T(p.Asp1049Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00251 in 1,613,954 control chromosomes in the GnomAD database, including 107 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.014 ( 48 hom., cov: 32)
Exomes 𝑓: 0.0014 ( 59 hom. )
Consequence
FLT4
NM_182925.5 synonymous
NM_182925.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.0530
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.47).
BP6
Variant 5-180616439-G-A is Benign according to our data. Variant chr5-180616439-G-A is described in ClinVar as [Benign]. Clinvar id is 263043.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-180616439-G-A is described in Lovd as [Benign].
BP7
Synonymous conserved (PhyloP=-0.053 with no splicing effect.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0136 (2067/152312) while in subpopulation AFR AF= 0.0465 (1934/41550). AF 95% confidence interval is 0.0448. There are 48 homozygotes in gnomad4. There are 983 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 48 AD,AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
FLT4 | NM_182925.5 | c.3147C>T | p.Asp1049Asp | synonymous_variant | 23/30 | ENST00000261937.11 | NP_891555.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
FLT4 | ENST00000261937.11 | c.3147C>T | p.Asp1049Asp | synonymous_variant | 23/30 | 1 | NM_182925.5 | ENSP00000261937.6 |
Frequencies
GnomAD3 genomes AF: 0.0135 AC: 2057AN: 152194Hom.: 47 Cov.: 32
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GnomAD3 exomes AF: 0.00326 AC: 820AN: 251186Hom.: 21 AF XY: 0.00249 AC XY: 339AN XY: 135882
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GnomAD4 exome AF: 0.00136 AC: 1984AN: 1461642Hom.: 59 Cov.: 34 AF XY: 0.00116 AC XY: 845AN XY: 727124
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GnomAD4 genome AF: 0.0136 AC: 2067AN: 152312Hom.: 48 Cov.: 32 AF XY: 0.0132 AC XY: 983AN XY: 74464
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ClinVar
Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Dec 11, 2020 | - - |
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Dec 31, 2019 | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Computational scores
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BayesDel_noAF
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CADD
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DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at