rs1423363607
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PM4
The NM_032043.3(BRIP1):c.333_334insTATCCA(p.Tyr110_Pro111dup) variant causes a inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000124 in 1,614,052 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. P111P) has been classified as Likely benign.
Frequency
Consequence
NM_032043.3 inframe_insertion
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BRIP1 | NM_032043.3 | c.333_334insTATCCA | p.Tyr110_Pro111dup | inframe_insertion | 4/20 | ENST00000259008.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BRIP1 | ENST00000259008.7 | c.333_334insTATCCA | p.Tyr110_Pro111dup | inframe_insertion | 4/20 | 1 | NM_032043.3 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152232Hom.: 0 Cov.: 32
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461820Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 727220
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152232Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74356
ClinVar
Submissions by phenotype
Hereditary cancer-predisposing syndrome Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | May 02, 2019 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 27, 2023 | The c.328_333dupTATCCA variant (also known as p.Y110_P111dup), located in coding exon 3 of the BRIP1 gene, results from an in-frame duplication of TATCCA at nucleotide positions 328 to 333. This results in the duplication of 2 extra residues (YP) between codons 110 and 111. This amino acid region is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive (Choi Y et al. PLoS ONE. 2012; 7(10):e46688). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Familial cancer of breast;C1836860:Fanconi anemia complementation group J Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 30, 2024 | This variant, c.328_333dup, results in the insertion of 2 amino acid(s) of the BRIP1 protein (p.Tyr110_Pro111dup), but otherwise preserves the integrity of the reading frame. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with BRIP1-related conditions. ClinVar contains an entry for this variant (Variation ID: 491465). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at