chr2-118103297-T-C
Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2
The NM_016133.4(INSIG2):c.345T>C(p.Phe115=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00466 in 1,613,400 control chromosomes in the GnomAD database, including 34 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.0044 ( 4 hom., cov: 32)
Exomes 𝑓: 0.0047 ( 30 hom. )
Consequence
INSIG2
NM_016133.4 synonymous
NM_016133.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 2.28
Genes affected
INSIG2 (HGNC:20452): (insulin induced gene 2) The protein encoded by this gene is highly similar to the protein product encoded by gene INSIG1. Both INSIG1 protein and this protein are endoplasmic reticulum proteins that block the processing of sterol regulatory element binding proteins (SREBPs) by binding to SREBP cleavage-activating protein (SCAP), and thus prevent SCAP from escorting SREBPs to the Golgi. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -15 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.6).
BP6
?
Variant 2-118103297-T-C is Benign according to our data. Variant chr2-118103297-T-C is described in ClinVar as [Benign]. Clinvar id is 770694.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=2.28 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.00469 (6848/1461094) while in subpopulation MID AF= 0.0368 (212/5764). AF 95% confidence interval is 0.0327. There are 30 homozygotes in gnomad4_exome. There are 3467 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd at 4 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
INSIG2 | NM_016133.4 | c.345T>C | p.Phe115= | synonymous_variant | 3/6 | ENST00000245787.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
INSIG2 | ENST00000245787.9 | c.345T>C | p.Phe115= | synonymous_variant | 3/6 | 1 | NM_016133.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00441 AC: 671AN: 152188Hom.: 4 Cov.: 32
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GnomAD3 exomes AF: 0.00475 AC: 1193AN: 251130Hom.: 6 AF XY: 0.00498 AC XY: 676AN XY: 135722
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GnomAD4 exome AF: 0.00469 AC: 6848AN: 1461094Hom.: 30 Cov.: 31 AF XY: 0.00477 AC XY: 3467AN XY: 726880
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GnomAD4 genome ? AF: 0.00440 AC: 670AN: 152306Hom.: 4 Cov.: 32 AF XY: 0.00439 AC XY: 327AN XY: 74482
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Dec 31, 2019 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at