rs201018893
Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 1P and 16B. PP3BP6_Very_StrongBS1BS2
The NM_014425.5(INVS):c.3017-5T>G variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00251 in 1,614,094 control chromosomes in the GnomAD database, including 23 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Consequence
NM_014425.5 splice_region, splice_polypyrimidine_tract, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -15 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
INVS | NM_014425.5 | c.3017-5T>G | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ENST00000262457.7 | |||
INVS | NM_001318381.2 | c.2729-5T>G | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ||||
INVS | NM_001318382.2 | c.2039-5T>G | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ||||
INVS | NR_134606.2 | n.3166-5T>G | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
INVS | ENST00000262457.7 | c.3017-5T>G | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_014425.5 | A2 | |||
INVS | ENST00000262456.6 | c.2507-5T>G | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 5 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.00202 AC: 307AN: 152180Hom.: 2 Cov.: 33
GnomAD3 exomes AF: 0.00276 AC: 695AN: 251466Hom.: 7 AF XY: 0.00338 AC XY: 459AN XY: 135902
GnomAD4 exome AF: 0.00256 AC: 3738AN: 1461796Hom.: 21 Cov.: 31 AF XY: 0.00287 AC XY: 2084AN XY: 727202
GnomAD4 genome ? AF: 0.00202 AC: 307AN: 152298Hom.: 2 Cov.: 33 AF XY: 0.00238 AC XY: 177AN XY: 74466
ClinVar
Submissions by phenotype
not specified Benign:2
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Infantile nephronophthisis Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. - |
Likely benign, criteria provided, single submitter | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | Jun 28, 2017 | - - |
Nephronophthisis Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
not provided Benign:1
Likely benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at