rs2070872
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Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1
The NM_000918.4(P4HB):c.855+102T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.21 in 1,449,520 control chromosomes in the GnomAD database, including 34,821 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.26 ( 5769 hom., cov: 33)
Exomes 𝑓: 0.20 ( 29052 hom. )
Consequence
P4HB
NM_000918.4 intron
NM_000918.4 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.801
Genes affected
P4HB (HGNC:8548): (prolyl 4-hydroxylase subunit beta) This gene encodes the beta subunit of prolyl 4-hydroxylase, a highly abundant multifunctional enzyme that belongs to the protein disulfide isomerase family. When present as a tetramer consisting of two alpha and two beta subunits, this enzyme is involved in hydroxylation of prolyl residues in preprocollagen. This enzyme is also a disulfide isomerase containing two thioredoxin domains that catalyze the formation, breakage and rearrangement of disulfide bonds. Other known functions include its ability to act as a chaperone that inhibits aggregation of misfolded proteins in a concentration-dependent manner, its ability to bind thyroid hormone, its role in both the influx and efflux of S-nitrosothiol-bound nitric oxide, and its function as a subunit of the microsomal triglyceride transfer protein complex. [provided by RefSeq, Jul 2008]
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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=-0.91).
BP6
?
Variant 17-81846845-A-G is Benign according to our data. Variant chr17-81846845-A-G is described in ClinVar as [Benign]. Clinvar id is 1273968.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.386 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
P4HB | NM_000918.4 | c.855+102T>C | intron_variant | ENST00000331483.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
P4HB | ENST00000331483.9 | c.855+102T>C | intron_variant | 1 | NM_000918.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.257 AC: 39041AN: 151994Hom.: 5753 Cov.: 33
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GnomAD4 exome AF: 0.204 AC: 264892AN: 1297406Hom.: 29052 Cov.: 19 AF XY: 0.200 AC XY: 129960AN XY: 649252
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GnomAD4 genome ? AF: 0.257 AC: 39093AN: 152114Hom.: 5769 Cov.: 33 AF XY: 0.255 AC XY: 18948AN XY: 74380
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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 | Mar 31, 2019 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at