rs4072924
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_006261.5(PROP1):c.109+3G>A variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.541 in 1,611,710 control chromosomes in the GnomAD database, including 238,286 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.54 ( 22452 hom., cov: 34)
Exomes 𝑓: 0.54 ( 215834 hom. )
Consequence
PROP1
NM_006261.5 splice_donor_region, intron
NM_006261.5 splice_donor_region, intron
Scores
2
Splicing: ADA: 0.0001374
2
Clinical Significance
Conservation
PhyloP100: 0.208
Genes affected
PROP1 (HGNC:9455): (PROP paired-like homeobox 1) This gene encodes a paired-like homeodomain transcription factor in the developing pituitary gland. Expression occurs prior to and is required for expression of pou domain transcription factor 1, which is responsible for pituitary development and hormone expression. Mutations in this gene have been associated with combined pituitary hormone deficiency-2 as well as deficiencies in luteinizing hormone, follicle-stimulating hormone, growth hormone, prolactin, and thyroid-stimulating hormone. [provided by RefSeq, Sep 2011]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.47).
BP6
?
Variant 5-177995822-C-T is Benign according to our data. Variant chr5-177995822-C-T is described in ClinVar as [Benign]. Clinvar id is 353016.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-177995822-C-T is described in Lovd as [Benign].
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.568 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PROP1 | NM_006261.5 | c.109+3G>A | splice_donor_region_variant, intron_variant | ENST00000308304.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PROP1 | ENST00000308304.2 | c.109+3G>A | splice_donor_region_variant, intron_variant | 1 | NM_006261.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.541 AC: 82161AN: 151998Hom.: 22441 Cov.: 34
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GnomAD3 exomes AF: 0.507 AC: 127052AN: 250828Hom.: 32756 AF XY: 0.503 AC XY: 68262AN XY: 135626
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GnomAD4 exome AF: 0.541 AC: 789333AN: 1459594Hom.: 215834 Cov.: 36 AF XY: 0.537 AC XY: 390082AN XY: 726232
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GnomAD4 genome ? AF: 0.540 AC: 82215AN: 152116Hom.: 22452 Cov.: 34 AF XY: 0.534 AC XY: 39731AN XY: 74360
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ClinVar
Significance: Benign
Submissions summary: Benign:7
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Pituitary hormone deficiency, combined, 2 Benign:3
Benign, no assertion criteria provided | clinical testing | Natera, Inc. | Sep 16, 2020 | - - |
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 benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 10, 2021 | - - |
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Jul 27, 2017 | - - |
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Mar 29, 2016 | Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency - |
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Aug 09, 2018 | - - |
Computational scores
Source:
Name
Calibrated prediction
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at