rs6172
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The ENST00000323322.10(GH1):c.-38A>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0237 in 1,613,064 control chromosomes in the GnomAD database, including 548 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.021 ( 42 hom., cov: 32)
Exomes 𝑓: 0.024 ( 506 hom. )
Consequence
GH1
ENST00000323322.10 5_prime_UTR
ENST00000323322.10 5_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.334
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=-0.87).
BP6
Variant 17-63918814-T-G is Benign according to our data. Variant chr17-63918814-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 891384.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0215 (3270/152178) while in subpopulation NFE AF= 0.0267 (1818/67988). AF 95% confidence interval is 0.0257. There are 42 homozygotes in gnomad4. There are 1541 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 42 AD,AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
GH1 | NM_000515.5 | c.-38A>C | 5_prime_UTR_variant | 1/5 | ENST00000323322.10 | NP_000506.2 | ||
GH1 | NM_022559.4 | c.-38A>C | 5_prime_UTR_variant | 1/5 | NP_072053.1 | |||
GH1 | NM_022560.4 | c.-38A>C | 5_prime_UTR_variant | 1/4 | NP_072054.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
GH1 | ENST00000323322.10 | c.-38A>C | 5_prime_UTR_variant | 1/5 | 1 | NM_000515.5 | ENSP00000312673 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0215 AC: 3262AN: 152060Hom.: 42 Cov.: 32
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GnomAD3 exomes AF: 0.0197 AC: 4953AN: 250918Hom.: 70 AF XY: 0.0199 AC XY: 2701AN XY: 135628
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GnomAD4 exome AF: 0.0240 AC: 35033AN: 1460886Hom.: 506 Cov.: 35 AF XY: 0.0238 AC XY: 17274AN XY: 726764
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GnomAD4 genome AF: 0.0215 AC: 3270AN: 152178Hom.: 42 Cov.: 32 AF XY: 0.0207 AC XY: 1541AN XY: 74430
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 19, 2021 | See Variant Classification Assertion Criteria. - |
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Decreased response to growth hormone stimulation test Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 18, 2018 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign. - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
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