GeneBe

rs2227589

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_000488.4(SERPINC1):​c.41+141G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

SERPINC1
NM_000488.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.894

Publications

46 publications found
Variant links:
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]
SERPINC1 Gene-Disease associations (from GenCC):
  • hereditary antithrombin deficiency
    Inheritance: AD, AR, SD Classification: DEFINITIVE, STRONG, SUPPORTIVE, LIMITED Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics, Genomics England PanelApp, ClinGen

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.77).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SERPINC1NM_000488.4 linkc.41+141G>T intron_variant Intron 1 of 6 ENST00000367698.4 NP_000479.1 P01008A0A024R944

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SERPINC1ENST00000367698.4 linkc.41+141G>T intron_variant Intron 1 of 6 1 NM_000488.4 ENSP00000356671.3 P01008
SERPINC1ENST00000494024.1 linkn.98+141G>T intron_variant Intron 1 of 3 3
ENSG00000305649ENST00000812169.1 linkn.118+138C>A intron_variant Intron 1 of 2
ENSG00000305649ENST00000812170.1 linkn.71+138C>A intron_variant Intron 1 of 1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
602202
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
321152
African (AFR)
AF:
0.00
AC:
0
AN:
16990
American (AMR)
AF:
0.00
AC:
0
AN:
33254
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
18612
East Asian (EAS)
AF:
0.00
AC:
0
AN:
33514
South Asian (SAS)
AF:
0.00
AC:
0
AN:
60706
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
47918
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
2754
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
356792
Other (OTH)
AF:
0.00
AC:
0
AN:
31662
GnomAD4 genome
Cov.:
32
Alfa
AF:
0.00
Hom.:
1110

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.77
CADD
Benign
1.7
DANN
Benign
0.70
PhyloP100
-0.89
PromoterAI
-0.12
Neutral

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs2227589; hg19: chr1-173886216; API