rs6220
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Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1
The NM_000618.5(IGF1):c.*1770C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.669 in 151,930 control chromosomes in the GnomAD database, including 34,277 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.67 ( 34277 hom., cov: 31)
Failed GnomAD Quality Control
Consequence
IGF1
NM_000618.5 3_prime_UTR
NM_000618.5 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.633
Genes affected
IGF1 (HGNC:5464): (insulin like growth factor 1) The protein encoded by this gene is similar to insulin in function and structure and is a member of a family of proteins involved in mediating growth and development. The encoded protein is processed from a precursor, bound by a specific receptor, and secreted. Defects in this gene are a cause of insulin-like growth factor I deficiency. Alternative splicing results in multiple transcript variants encoding different isoforms that may undergo similar processing to generate mature protein. [provided by RefSeq, Sep 2015]
HELLPAR (HGNC:43984): (HELLP associated long non-coding RNA)
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.9).
BP6
?
Variant 12-102400737-G-A is Benign according to our data. Variant chr12-102400737-G-A is described in ClinVar as [Benign]. Clinvar id is 306892.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
?
GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.724 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
IGF1 | NM_000618.5 | c.*1770C>T | 3_prime_UTR_variant | 4/4 | ENST00000337514.11 | ||
LINC02456 | XR_007063427.1 | n.697-3376G>A | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
IGF1 | ENST00000337514.11 | c.*1770C>T | 3_prime_UTR_variant | 4/4 | 1 | NM_000618.5 | P1 | ||
HELLPAR | ENST00000626826.1 | n.203153G>A | non_coding_transcript_exon_variant | 1/1 | |||||
LINC02456 | ENST00000704346.1 | n.1067-22334G>A | intron_variant, non_coding_transcript_variant | ||||||
LINC02456 | ENST00000635615.1 | n.450-22334G>A | intron_variant, non_coding_transcript_variant | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.669 AC: 101625AN: 151812Hom.: 34283 Cov.: 31
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GnomAD4 exome Data not reliable, filtered out with message: AC0AC: 0AN: 0Hom.: 0 Cov.: 0AC XY: 0AN XY: 0
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GnomAD4 genome ? AF: 0.669 AC: 101647AN: 151930Hom.: 34277 Cov.: 31 AF XY: 0.669 AC XY: 49690AN XY: 74256
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Growth delay due to insulin-like growth factor type 1 deficiency Benign:1
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. - |
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