chr17-63917495-A-G
Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6BP7BS1
The NM_000515.5(GH1):c.468T>C(p.Asp156=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000154 in 1,613,968 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.00018 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00015 ( 3 hom. )
Consequence
GH1
NM_000515.5 synonymous
NM_000515.5 synonymous
Scores
1
6
Clinical Significance
Conservation
PhyloP100: -3.80
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 -10 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.013378203).
BP6
?
Variant 17-63917495-A-G is Benign according to our data. Variant chr17-63917495-A-G is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 891325.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=2, Uncertain_significance=1}.
BP7
?
Synonymous conserved (PhyloP=-3.8 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000177 (27/152302) while in subpopulation EAS AF= 0.000966 (5/5176). AF 95% confidence interval is 0.00038. There are 0 homozygotes in gnomad4. There are 13 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GH1 | NM_000515.5 | c.468T>C | p.Asp156= | synonymous_variant | 5/5 | ENST00000323322.10 | |
LOC112268204 | XR_002958148.2 | n.341-102A>G | intron_variant, non_coding_transcript_variant | ||||
GH1 | NM_022559.4 | c.423T>C | p.Asp141= | synonymous_variant | 5/5 | ||
GH1 | NM_022560.4 | c.348T>C | p.Asp116= | synonymous_variant | 4/4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GH1 | ENST00000323322.10 | c.468T>C | p.Asp156= | synonymous_variant | 5/5 | 1 | NM_000515.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000171 AC: 26AN: 152184Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000239 AC: 60AN: 251168Hom.: 1 AF XY: 0.000228 AC XY: 31AN XY: 135738
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GnomAD4 exome AF: 0.000151 AC: 221AN: 1461666Hom.: 3 Cov.: 31 AF XY: 0.000166 AC XY: 121AN XY: 727144
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:2
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jul 18, 2023 | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Dec 01, 2022 | GH1: BP4, BP7 - |
Decreased response to growth hormone stimulation test Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
FATHMM_MKL
Benign
N
MetaRNN
Benign
T
MutationTaster
Benign
D;D;D;D;D
Sift4G
Pathogenic
D
Polyphen
B
Vest4
MVP
GERP RS
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