chr17-63918780-A-C
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_000515.5(GH1):c.-4T>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0417 in 1,606,548 control chromosomes in the GnomAD database, including 1,831 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.055 ( 335 hom., cov: 32)
Exomes 𝑓: 0.040 ( 1496 hom. )
Consequence
GH1
NM_000515.5 5_prime_UTR
NM_000515.5 5_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.0460
Genes affected
GH1 (HGNC:4261): (growth hormone 1) The protein encoded by this gene is a member of the somatotropin/prolactin family of hormones which play an important role in growth control. The gene, along with four other related genes, is located at the growth hormone locus on chromosome 17 where they are interspersed in the same transcriptional orientation; an arrangement which is thought to have evolved by a series of gene duplications. The five genes share a remarkably high degree of sequence identity. Alternative splicing generates additional isoforms of each of the five growth hormones, leading to further diversity and potential for specialization. This particular family member is expressed in the pituitary but not in placental tissue as is the case for the other four genes in the growth hormone locus. Mutations in or deletions of the gene lead to growth hormone deficiency and short stature. [provided by RefSeq, Jul 2008]
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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=-0.85).
BP6
?
Variant 17-63918780-A-C is Benign according to our data. Variant chr17-63918780-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 324460.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.1 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GH1 | NM_000515.5 | c.-4T>G | 5_prime_UTR_variant | 1/5 | ENST00000323322.10 | ||
GH1 | NM_022559.4 | c.-4T>G | 5_prime_UTR_variant | 1/5 | |||
GH1 | NM_022560.4 | c.-4T>G | 5_prime_UTR_variant | 1/4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GH1 | ENST00000323322.10 | c.-4T>G | 5_prime_UTR_variant | 1/5 | 1 | NM_000515.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0548 AC: 8328AN: 152082Hom.: 335 Cov.: 32
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GnomAD3 exomes AF: 0.0360 AC: 8968AN: 249454Hom.: 254 AF XY: 0.0350 AC XY: 4720AN XY: 134946
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GnomAD4 exome AF: 0.0403 AC: 58640AN: 1454348Hom.: 1496 Cov.: 35 AF XY: 0.0394 AC XY: 28508AN XY: 723706
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GnomAD4 genome ? AF: 0.0548 AC: 8338AN: 152200Hom.: 335 Cov.: 32 AF XY: 0.0528 AC XY: 3932AN XY: 74430
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Autosomal dominant isolated somatotropin deficiency;C0342573:Ateleiotic dwarfism;C1849779:Short stature due to growth hormone qualitative anomaly;C2748571:Isolated growth hormone deficiency type IB Benign:1
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Jun 29, 2017 | - - |
GH1-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | May 17, 2019 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Oct 15, 2018 | - - |
Decreased response to growth hormone stimulation test Benign:1
Likely 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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. - |
Computational scores
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BayesDel_noAF
Benign
Cadd
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Dann
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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