rs373264811
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Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 2P and 12B. PM2BP4_StrongBP6_Very_Strong
The NM_014425.5(INVS):c.1079-13G>C 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 0.0000459 in 1,613,792 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000048 ( 0 hom. )
Consequence
INVS
NM_014425.5 splice_polypyrimidine_tract, intron
NM_014425.5 splice_polypyrimidine_tract, intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.0260
Genes affected
INVS (HGNC:17870): (inversin) This gene encodes a protein containing multiple ankyrin domains and two IQ calmodulin-binding domains. The encoded protein may function in renal tubular development and function, and in left-right axis determination. This protein interacts with nephrocystin and infers a connection between primary cilia function and left-right axis determination. A similar protein in mice interacts with calmodulin. Mutations in this gene have been associated with nephronophthisis type 2. Multiple transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, May 2012]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -10 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.85).
BP6
?
Variant 9-100252270-G-C is Benign according to our data. Variant chr9-100252270-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 260404.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
INVS | NM_014425.5 | c.1079-13G>C | splice_polypyrimidine_tract_variant, intron_variant | ENST00000262457.7 | |||
INVS | NM_001318381.2 | c.791-13G>C | splice_polypyrimidine_tract_variant, intron_variant | ||||
INVS | NM_001318382.2 | c.101-13G>C | splice_polypyrimidine_tract_variant, intron_variant | ||||
INVS | NR_134606.2 | n.1277-13G>C | 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.1079-13G>C | splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_014425.5 | A2 | |||
INVS | ENST00000262456.6 | c.1079-13G>C | splice_polypyrimidine_tract_variant, intron_variant | 5 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152158Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000558 AC: 14AN: 250788Hom.: 0 AF XY: 0.0000738 AC XY: 10AN XY: 135526
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GnomAD4 exome AF: 0.0000479 AC: 70AN: 1461516Hom.: 0 Cov.: 32 AF XY: 0.0000536 AC XY: 39AN XY: 727086
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GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152276Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74450
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Nephronophthisis Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 11, 2023 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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