rs2241028
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Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1
The NM_013247.5(HTRA2):c.1046-49G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0612 in 1,612,272 control chromosomes in the GnomAD database, including 3,680 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.051 ( 267 hom., cov: 32)
Exomes 𝑓: 0.062 ( 3413 hom. )
Consequence
HTRA2
NM_013247.5 intron
NM_013247.5 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.0200
Genes affected
HTRA2 (HGNC:14348): (HtrA serine peptidase 2) This gene encodes a serine protease. The protein has been localized in the endoplasmic reticulum and interacts with an alternatively spliced form of mitogen-activated protein kinase 14. The protein has also been localized to the mitochondria with release to the cytosol following apoptotic stimulus. The protein is thought to induce apoptosis by binding the apoptosis inhibitory protein baculoviral IAP repeat-containing 4. Nuclear localization of this protein has also been observed. Alternate splicing of this gene results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Mar 2016]
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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=-0.87).
BP6
?
Variant 2-74531807-G-A is Benign according to our data. Variant chr2-74531807-G-A is described in ClinVar as [Benign]. Clinvar id is 671226.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
?
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.155 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HTRA2 | NM_013247.5 | c.1046-49G>A | intron_variant | ENST00000258080.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HTRA2 | ENST00000258080.8 | c.1046-49G>A | intron_variant | 1 | NM_013247.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0507 AC: 7710AN: 152112Hom.: 267 Cov.: 32
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GnomAD3 exomes AF: 0.0613 AC: 15377AN: 250944Hom.: 655 AF XY: 0.0639 AC XY: 8667AN XY: 135632
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GnomAD4 exome AF: 0.0623 AC: 91032AN: 1460042Hom.: 3413 Cov.: 32 AF XY: 0.0633 AC XY: 45994AN XY: 726370
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GnomAD4 genome ? AF: 0.0506 AC: 7707AN: 152230Hom.: 267 Cov.: 32 AF XY: 0.0528 AC XY: 3932AN XY: 74434
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 14, 2018 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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