rs677
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_000488.4(SERPINC1):c.1218+27G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.118 in 1,567,420 control chromosomes in the GnomAD database, including 12,135 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★★).
Frequency
Genomes: 𝑓 0.096 ( 965 hom., cov: 31)
Exomes 𝑓: 0.12 ( 11170 hom. )
Consequence
SERPINC1
NM_000488.4 intron
NM_000488.4 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.64
Genes affected
SERPINC1 (HGNC:775): (serpin family C member 1) The protein encoded by this gene, antithrombin III, is a plasma protease inhibitor and a member of the serpin superfamily. This protein inhibits thrombin as well as other activated serine proteases of the coagulation system, and it regulates the blood coagulation cascade. The protein includes two functional domains: the heparin binding-domain at the N-terminus of the mature protein, and the reactive site domain at the C-terminus. The inhibitory activity is enhanced by the presence of heparin. Numerous mutations have been identified for this gene, many of which are known to cause antithrombin-III deficiency which constitutes a strong risk factor for thrombosis. A reduction in the serum level of this protein is associated with severe cases of Coronavirus Disease 19 (COVID-19). [provided by RefSeq, Sep 2020]
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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=-0.93).
BP6
?
Variant 1-173907423-C-G is Benign according to our data. Variant chr1-173907423-C-G is described in ClinVar as [Benign]. Clinvar id is 1261351.Status of the report is reviewed_by_expert_panel, 3 stars.
BA1
?
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.231 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SERPINC1 | NM_000488.4 | c.1218+27G>C | intron_variant | ENST00000367698.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SERPINC1 | ENST00000367698.4 | c.1218+27G>C | intron_variant | 1 | NM_000488.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0963 AC: 14643AN: 152024Hom.: 967 Cov.: 31
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GnomAD3 exomes AF: 0.125 AC: 31403AN: 251440Hom.: 2339 AF XY: 0.130 AC XY: 17684AN XY: 135888
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GnomAD4 exome AF: 0.120 AC: 170307AN: 1415278Hom.: 11170 Cov.: 24 AF XY: 0.123 AC XY: 86644AN XY: 706802
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GnomAD4 genome ? AF: 0.0962 AC: 14640AN: 152142Hom.: 965 Cov.: 31 AF XY: 0.0964 AC XY: 7166AN XY: 74374
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ClinVar
Significance: Benign
Submissions summary: Benign:3
Revision: reviewed by expert panel
LINK: link
Submissions by phenotype
Hereditary antithrombin deficiency Benign:2
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 15, 2021 | - - |
Benign, reviewed by expert panel | curation | Clingen Thrombosis Variant Curation Expert Panel, ClinGen | Jul 25, 2023 | The NM_000488.4:c.1218+27G>C variant is reported at an Popmax FAF MAF of 0.2409 (4979/19948 alleles) in the East Asian population in the genomes in gnomAD v2.1.1 with a total of 2550 homozygotes, meeting BA1 criteria of FAF >= 0.002. The variant is not predicted to cause a splicing impact by by SpliceAI and VARSEAK, and the nucleotide is not conserved with a PhyloP score of -1.65 and a PhastCons score of ~0. In summary, this variant meets criteria to be classified as benign. ACMG/AMP criteria applied, as specified by the Thrombosis Variant Curation Expert Panel for SERPINC1: BA1, BP4, BP7. - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 12, 2018 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
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