chr3-25461184-C-G
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Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2
The NM_000965.5(RARB):c.158-9C>G variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00123 in 1,602,584 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 0.0065 ( 9 hom., cov: 32)
Exomes 𝑓: 0.00068 ( 14 hom. )
Consequence
RARB
NM_000965.5 splice_polypyrimidine_tract, intron
NM_000965.5 splice_polypyrimidine_tract, intron
Scores
2
Splicing: ADA: 0.001116
2
Clinical Significance
Conservation
PhyloP100: 0.185
Genes affected
RARB (HGNC:9865): (retinoic acid receptor beta) This gene encodes retinoic acid receptor beta, a member of the thyroid-steroid hormone receptor superfamily of nuclear transcriptional regulators. This receptor localizes to the cytoplasm and to subnuclear compartments. It binds retinoic acid, the biologically active form of vitamin A which mediates cellular signalling in embryonic morphogenesis, cell growth and differentiation. It is thought that this protein limits growth of many cell types by regulating gene expression. The gene was first identified in a hepatocellular carcinoma where it flanks a hepatitis B virus integration site. Alternate promoter usage and differential splicing result in multiple transcript variants. [provided by RefSeq, Mar 2014]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.82).
BP6
Variant 3-25461184-C-G is Benign according to our data. Variant chr3-25461184-C-G is described in ClinVar as [Benign]. Clinvar id is 707589.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00651 (992/152308) while in subpopulation AFR AF= 0.0226 (941/41558). AF 95% confidence interval is 0.0214. There are 9 homozygotes in gnomad4. There are 484 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 9 AD,AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
RARB | NM_000965.5 | c.158-9C>G | splice_polypyrimidine_tract_variant, intron_variant | ENST00000330688.9 | NP_000956.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
RARB | ENST00000330688.9 | c.158-9C>G | splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_000965.5 | ENSP00000332296 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00652 AC: 993AN: 152190Hom.: 9 Cov.: 32
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GnomAD3 exomes AF: 0.00170 AC: 410AN: 241074Hom.: 7 AF XY: 0.00106 AC XY: 138AN XY: 130338
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GnomAD4 exome AF: 0.000677 AC: 982AN: 1450276Hom.: 14 Cov.: 31 AF XY: 0.000527 AC XY: 380AN XY: 720994
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GnomAD4 genome AF: 0.00651 AC: 992AN: 152308Hom.: 9 Cov.: 32 AF XY: 0.00650 AC XY: 484AN XY: 74480
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Microphthalmia, syndromic 12 Benign:1
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Nov 15, 2023 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at