rs10200271
Positions:
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1
The NM_001017915.3(INPP5D):c.665+1699A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0389 in 152,126 control chromosomes in the GnomAD database, including 139 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: 𝑓 0.039 ( 139 hom., cov: 32)
Consequence
INPP5D
NM_001017915.3 intron
NM_001017915.3 intron
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -2.01
Genes affected
INPP5D (HGNC:6079): (inositol polyphosphate-5-phosphatase D) This gene is a member of the inositol polyphosphate-5-phosphatase (INPP5) family and encodes a protein with an N-terminal SH2 domain, an inositol phosphatase domain, and two C-terminal protein interaction domains. Expression of this protein is restricted to hematopoietic cells where its movement from the cytosol to the plasma membrane is mediated by tyrosine phosphorylation. At the plasma membrane, the protein hydrolyzes the 5' phosphate from phosphatidylinositol (3,4,5)-trisphosphate and inositol-1,3,4,5-tetrakisphosphate, thereby affecting multiple signaling pathways. The protein is also partly localized to the nucleus, where it may be involved in nuclear inositol phosphate signaling processes. Overall, the protein functions as a negative regulator of myeloid cell proliferation and survival. Mutations in this gene are associated with defects and cancers of the immune system. Deficiencies in the encoded protein, SHIP1, have been associated with Inflammatory Bowel Disease types such as Crohn's Disease and Ulcerative Colitis. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Jul 2020]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -12 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-1.04).
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.053 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
INPP5D | NM_001017915.3 | c.665+1699A>C | intron_variant | ENST00000445964.6 | |||
INPP5D | NM_005541.5 | c.662+1699A>C | intron_variant | ||||
INPP5D | XM_047444219.1 | c.665+1699A>C | intron_variant | ||||
INPP5D | XM_047444220.1 | c.662+1699A>C | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
INPP5D | ENST00000445964.6 | c.665+1699A>C | intron_variant | 1 | NM_001017915.3 | P5 | |||
INPP5D | ENST00000359570.9 | c.662+1699A>C | intron_variant | 1 | A2 | ||||
INPP5D | ENST00000451407.4 | n.778+1699A>C | intron_variant, non_coding_transcript_variant | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0389 AC: 5913AN: 152008Hom.: 138 Cov.: 32
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We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome ? AF: 0.0389 AC: 5919AN: 152126Hom.: 139 Cov.: 32 AF XY: 0.0372 AC XY: 2767AN XY: 74404
GnomAD4 genome
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3478
ClinVar
Not reported inComputational scores
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Name
Calibrated prediction
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Prediction
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