12-48979522-G-A
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Variant summary
Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS1
The NM_005430.4(WNT1):c.159G>A(p.Leu53=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000133 in 1,613,968 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00051 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000094 ( 1 hom. )
Consequence
WNT1
NM_005430.4 synonymous
NM_005430.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.61
Genes affected
WNT1 (HGNC:12774): (Wnt family member 1) The WNT gene family consists of structurally related genes which encode secreted signaling proteins. These proteins have been implicated in oncogenesis and in several developmental processes, including regulation of cell fate and patterning during embryogenesis. This gene is a member of the WNT gene family. It is very conserved in evolution, and the protein encoded by this gene is known to be 98% identical to the mouse Wnt1 protein at the amino acid level. The studies in mouse indicate that the Wnt1 protein functions in the induction of the mesencephalon and cerebellum. This gene was originally considered as a candidate gene for Joubert syndrome, an autosomal recessive disorder with cerebellar hypoplasia as a leading feature. However, further studies suggested that the gene mutations might not have a significant role in Joubert syndrome. This gene is clustered with another family member, WNT10B, in the chromosome 12q13 region. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -17 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.55).
BP6
Variant 12-48979522-G-A is Benign according to our data. Variant chr12-48979522-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 746994.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=1.62 with no splicing effect.
BS1
Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.000506 (77/152312) while in subpopulation AMR AF= 0.00425 (65/15306). AF 95% confidence interval is 0.00342. There are 0 homozygotes in gnomad4. There are 35 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
WNT1 | NM_005430.4 | c.159G>A | p.Leu53= | synonymous_variant | 2/4 | ENST00000293549.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
WNT1 | ENST00000293549.4 | c.159G>A | p.Leu53= | synonymous_variant | 2/4 | 1 | NM_005430.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000506 AC: 77AN: 152194Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000283 AC: 71AN: 251088Hom.: 0 AF XY: 0.000250 AC XY: 34AN XY: 135826
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GnomAD4 exome AF: 0.0000944 AC: 138AN: 1461656Hom.: 1 Cov.: 31 AF XY: 0.0000990 AC XY: 72AN XY: 727142
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GnomAD4 genome AF: 0.000506 AC: 77AN: 152312Hom.: 0 Cov.: 33 AF XY: 0.000470 AC XY: 35AN XY: 74482
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
WNT1-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Dec 04, 2019 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 28, 2024 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
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DANN
Benign
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at