rs117839740
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_000515.5(GH1):c.456+18G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000633 in 1,614,148 control chromosomes in the GnomAD database, including 15 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.00067 ( 2 hom., cov: 32)
Exomes 𝑓: 0.00063 ( 13 hom. )
Consequence
GH1
NM_000515.5 intron
NM_000515.5 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.134
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=-0.91).
BP6
?
Variant 17-63917742-C-A is Benign according to our data. Variant chr17-63917742-C-A is described in ClinVar as [Benign]. Clinvar id is 585936.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
?
Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00067 (102/152264) while in subpopulation EAS AF= 0.0189 (98/5180). AF 95% confidence interval is 0.0159. There are 2 homozygotes in gnomad4. There are 60 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd4 at 2 AD,AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GH1 | NM_000515.5 | c.456+18G>T | intron_variant | ENST00000323322.10 | |||
LOC112268204 | XR_002958148.2 | n.389-48C>A | intron_variant, non_coding_transcript_variant | ||||
GH1 | NM_022559.4 | c.411+18G>T | intron_variant | ||||
GH1 | NM_022560.4 | c.336+18G>T | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GH1 | ENST00000323322.10 | c.456+18G>T | intron_variant | 1 | NM_000515.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000670 AC: 102AN: 152146Hom.: 2 Cov.: 32
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GnomAD3 exomes AF: 0.00154 AC: 386AN: 251358Hom.: 1 AF XY: 0.00142 AC XY: 193AN XY: 135898
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GnomAD4 exome AF: 0.000629 AC: 920AN: 1461884Hom.: 13 Cov.: 35 AF XY: 0.000609 AC XY: 443AN XY: 727244
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GnomAD4 genome ? AF: 0.000670 AC: 102AN: 152264Hom.: 2 Cov.: 32 AF XY: 0.000806 AC XY: 60AN XY: 74460
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Feb 16, 2018 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jun 27, 2023 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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