chr16-289493-G-A
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_003502.4(AXIN1):c.2409C>T(p.Arg803=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00159 in 1,612,952 control chromosomes in the GnomAD database, including 23 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.0081 ( 13 hom., cov: 33)
Exomes 𝑓: 0.00091 ( 10 hom. )
Consequence
AXIN1
NM_003502.4 synonymous
NM_003502.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -2.15
Genes affected
AXIN1 (HGNC:903): (axin 1) This gene encodes a cytoplasmic protein which contains a regulation of G-protein signaling (RGS) domain and a dishevelled and axin (DIX) domain. The encoded protein interacts with adenomatosis polyposis coli, catenin beta-1, glycogen synthase kinase 3 beta, protein phosphate 2, and itself. This protein functions as a negative regulator of the wingless-type MMTV integration site family, member 1 (WNT) signaling pathway and can induce apoptosis. The crystal structure of a portion of this protein, alone and in a complex with other proteins, has been resolved. Mutations in this gene have been associated with hepatocellular carcinoma, hepatoblastomas, ovarian endometriod adenocarcinomas, and medullablastomas. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]
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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=-0.82).
BP6
?
Variant 16-289493-G-A is Benign according to our data. Variant chr16-289493-G-A is described in ClinVar as [Benign]. Clinvar id is 787969.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-2.15 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00815 (1241/152328) while in subpopulation AFR AF= 0.0279 (1158/41562). AF 95% confidence interval is 0.0265. There are 13 homozygotes in gnomad4. There are 606 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd at 13 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
AXIN1 | NM_003502.4 | c.2409C>T | p.Arg803= | synonymous_variant | 10/11 | ENST00000262320.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AXIN1 | ENST00000262320.8 | c.2409C>T | p.Arg803= | synonymous_variant | 10/11 | 1 | NM_003502.4 | A1 | |
AXIN1 | ENST00000354866.7 | c.2301C>T | p.Arg767= | synonymous_variant | 9/10 | 1 | P4 | ||
AXIN1 | ENST00000457798.1 | c.165C>T | p.Arg55= | synonymous_variant | 2/3 | 3 | |||
AXIN1 | ENST00000461023.5 | n.5478C>T | non_coding_transcript_exon_variant | 7/8 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.00815 AC: 1240AN: 152210Hom.: 13 Cov.: 33
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GnomAD3 exomes AF: 0.00232 AC: 580AN: 250010Hom.: 7 AF XY: 0.00160 AC XY: 217AN XY: 135670
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GnomAD4 exome AF: 0.000907 AC: 1325AN: 1460624Hom.: 10 Cov.: 33 AF XY: 0.000767 AC XY: 557AN XY: 726602
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Nov 30, 2021 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Dec 31, 2019 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
Cadd
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Dann
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at