chr11-57600106-G-A
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Variant summary
Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS1
The NM_000062.3(SERPING1):c.279G>A(p.Glu93=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000072 in 1,611,142 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.000086 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000071 ( 1 hom. )
Consequence
SERPING1
NM_000062.3 synonymous
NM_000062.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.565
Genes affected
SERPING1 (HGNC:1228): (serpin family G member 1) This gene encodes a highly glycosylated plasma protein involved in the regulation of the complement cascade. Its encoded protein, C1 inhibitor, inhibits activated C1r and C1s of the first complement component and thus regulates complement activation. It is synthesized in the liver, and its deficiency is associated with hereditary angioneurotic oedema (HANE). Alternative splicing results in multiple transcript variants encoding the same isoform. [provided by RefSeq, May 2020]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -17 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.88).
BP6
Variant 11-57600106-G-A is Benign according to our data. Variant chr11-57600106-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 403429.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-0.565 with no splicing effect.
BS1
Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.0000706 (103/1459782) while in subpopulation MID AF= 0.0052 (30/5764). AF 95% confidence interval is 0.00375. There are 1 homozygotes in gnomad4_exome. There are 45 alleles in male gnomad4_exome subpopulation. Median coverage is 34. This position pass quality control queck.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SERPING1 | NM_000062.3 | c.279G>A | p.Glu93= | synonymous_variant | 3/8 | ENST00000278407.9 | |
SERPING1 | NM_001032295.2 | c.279G>A | p.Glu93= | synonymous_variant | 2/7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SERPING1 | ENST00000278407.9 | c.279G>A | p.Glu93= | synonymous_variant | 3/8 | 1 | NM_000062.3 | P2 |
Frequencies
GnomAD3 genomes AF: 0.0000860 AC: 13AN: 151244Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000841 AC: 21AN: 249638Hom.: 0 AF XY: 0.0000741 AC XY: 10AN XY: 134930
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GnomAD4 exome AF: 0.0000706 AC: 103AN: 1459782Hom.: 1 Cov.: 34 AF XY: 0.0000620 AC XY: 45AN XY: 726272
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GnomAD4 genome AF: 0.0000859 AC: 13AN: 151360Hom.: 0 Cov.: 32 AF XY: 0.0000676 AC XY: 5AN XY: 73936
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ClinVar
Significance: Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Mar 28, 2016 | Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Silent variant not in splice consensus, gene associated with hereditary angioedma - |
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | May 15, 2022 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 16, 2024 | - - |
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