19-18386195-C-T
Variant names:
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7
The NM_004864.4(GDF15):c.6C>T(p.Pro2Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000184 in 1,610,994 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.00039 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00016 ( 0 hom. )
Consequence
GDF15
NM_004864.4 synonymous
NM_004864.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.20
Genes affected
GDF15 (HGNC:30142): (growth differentiation factor 15) This gene encodes a secreted ligand of the TGF-beta (transforming growth factor-beta) superfamily of proteins. Ligands of this family bind various TGF-beta receptors leading to recruitment and activation of SMAD family transcription factors that regulate gene expression. The encoded preproprotein is proteolytically processed to generate each subunit of the disulfide-linked homodimer. The protein is expressed in a broad range of cell types, acts as a pleiotropic cytokine and is involved in the stress response program of cells after cellular injury. Increased protein levels are associated with disease states such as tissue hypoxia, inflammation, acute injury and oxidative stress. [provided by RefSeq, Aug 2016]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -5 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.56).
BP6
Variant 19-18386195-C-T is Benign according to our data. Variant chr19-18386195-C-T is described in ClinVar as [Benign]. Clinvar id is 716361.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=-1.2 with no splicing effect.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
GDF15 | ENST00000252809.3 | c.6C>T | p.Pro2Pro | synonymous_variant | Exon 1 of 2 | 1 | NM_004864.4 | ENSP00000252809.3 | ||
GDF15 | ENST00000595973.3 | c.6C>T | p.Pro2Pro | synonymous_variant | Exon 2 of 3 | 5 | ENSP00000470531.3 | |||
GDF15 | ENST00000597765.2 | c.6C>T | p.Pro2Pro | synonymous_variant | Exon 2 of 3 | 4 | ENSP00000469819.2 |
Frequencies
GnomAD3 genomes AF: 0.000394 AC: 60AN: 152192Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000500 AC: 125AN: 249894Hom.: 0 AF XY: 0.000363 AC XY: 49AN XY: 135162
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GnomAD4 exome AF: 0.000162 AC: 236AN: 1458684Hom.: 0 Cov.: 29 AF XY: 0.000153 AC XY: 111AN XY: 725404
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GnomAD4 genome AF: 0.000394 AC: 60AN: 152310Hom.: 0 Cov.: 33 AF XY: 0.000376 AC XY: 28AN XY: 74468
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Jul 06, 2018
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
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Computational scores
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BayesDel_noAF
Benign
CADD
Benign
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