chr2-74958847-G-A
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Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS2
The NM_019896.4(POLE4):c.168G>A(p.Val56=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00678 in 1,561,440 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 Benign (★).
Frequency
Genomes: 𝑓 0.0050 ( 2 hom., cov: 33)
Exomes 𝑓: 0.0070 ( 42 hom. )
Consequence
POLE4
NM_019896.4 synonymous
NM_019896.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.598
Genes affected
POLE4 (HGNC:18755): (DNA polymerase epsilon 4, accessory subunit) POLE4 is a histone-fold protein that interacts with other histone-fold proteins to bind DNA in a sequence-independent manner. These histone-fold protein dimers combine within larger enzymatic complexes for DNA transcription, replication, and packaging.[supplied by OMIM, Apr 2004]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -9 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.33).
BP6
Variant 2-74958847-G-A is Benign according to our data. Variant chr2-74958847-G-A is described in ClinVar as [Benign]. Clinvar id is 774287.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=0.598 with no splicing effect.
BS2
High Homozygotes in GnomAd4 at 2 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
POLE4 | NM_019896.4 | c.168G>A | p.Val56= | synonymous_variant | 1/4 | ENST00000483063.2 | |
LOC105374809 | XR_002959406.2 | n.33C>T | non_coding_transcript_exon_variant | 1/2 | |||
LOC105374809 | XR_007087109.1 | n.33C>T | non_coding_transcript_exon_variant | 1/2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
POLE4 | ENST00000483063.2 | c.168G>A | p.Val56= | synonymous_variant | 1/4 | 1 | NM_019896.4 | P1 | |
POLE4 | ENST00000233699.8 | n.56G>A | non_coding_transcript_exon_variant | 1/5 | 3 | ||||
POLE4 | ENST00000459636.5 | n.142G>A | non_coding_transcript_exon_variant | 1/4 | 3 | ||||
POLE4 | ENST00000485527.5 | n.143G>A | non_coding_transcript_exon_variant | 1/3 | 2 |
Frequencies
GnomAD3 genomes AF: 0.00501 AC: 763AN: 152200Hom.: 2 Cov.: 33
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GnomAD3 exomes AF: 0.00466 AC: 788AN: 168988Hom.: 3 AF XY: 0.00460 AC XY: 414AN XY: 89912
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GnomAD4 exome AF: 0.00697 AC: 9824AN: 1409124Hom.: 42 Cov.: 34 AF XY: 0.00684 AC XY: 4763AN XY: 696152
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GnomAD4 genome AF: 0.00502 AC: 764AN: 152316Hom.: 2 Cov.: 33 AF XY: 0.00518 AC XY: 386AN XY: 74480
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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
Benign, criteria provided, single submitter | clinical testing | Invitae | Aug 07, 2018 | - - |
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