Variant chr1-173907567-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BA1BS2

This summary comes from the ClinGen Evidence Repository: The NM_000488.4:c.1154-53G>A variant is reported at a popmax FAF of 0.3028 and the highest MAF of 0.3263 (32%; 507/1554 alleles with 81 homozygotes) in the East Asian population in gnomAD v2.1.1, meeting criteria for BA1 (MAF >0.002). The variant is reported in 8 individuals with normal antithrombin levels. 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, BS2. LINK:https://erepo.genome.network/evrepo/ui/classification/CA10960823/MONDO:0013144/084

Frequency

Genomes: 𝑓 0.10 ( 950 hom., cov: 31)

Exomes 𝑓: 0.11 ( 8402 hom. )

Consequence

SERPINC1
NM_000488.4 intron

Scores

Clinical Significance

Benign reviewed by expert panel B:3

Conservation

PhyloP100: 0.0860

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BS2

BA1

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SERPINC1	NM_000488.4 linkuse as main transcript	c.1154-53G>A		intron_variant		ENST00000367698.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SERPINC1	ENST00000367698.4 linkuse as main transcript	c.1154-53G>A		intron_variant		1	NM_000488.4	P1

Frequencies

GnomAD3 genomes

AF:

0.100

AC:

15213

AN:

152108

Hom.:

950

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0643

Gnomad AMI

AF:

0.0989

Gnomad AMR

AF:

0.0870

Gnomad ASJ

AF:

0.158

Gnomad EAS

AF:

0.309

Gnomad SAS

AF:

0.141

Gnomad FIN

AF:

0.106

Gnomad MID

AF:

0.108

Gnomad NFE

AF:

0.102

Gnomad OTH

AF:

0.111

GnomAD4 exome

AF:

0.115

AC:

133561

AN:

1161880

Hom.:

8402

AF XY:

0.116

AC XY:

68918

AN XY:

592314

show subpopulations

Gnomad4 AFR exome

AF:

0.0638

Gnomad4 AMR exome

AF:

0.0522

Gnomad4 ASJ exome

AF:

0.152

Gnomad4 EAS exome

AF:

0.283

Gnomad4 SAS exome

AF:

0.149

Gnomad4 FIN exome

AF:

0.102

Gnomad4 NFE exome

AF:

0.108

Gnomad4 OTH exome

AF:

0.126

GnomAD4 genome

AF:

0.100

AC:

15219

AN:

152226

Hom.:

950

Cov.:

AF XY:

0.102

AC XY:

7585

AN XY:

74420

show subpopulations

Gnomad4 AFR

AF:

0.0642

Gnomad4 AMR

AF:

0.0869

Gnomad4 ASJ

AF:

0.158

Gnomad4 EAS

AF:

0.309

Gnomad4 SAS

AF:

0.141

Gnomad4 FIN

AF:

0.106

Gnomad4 NFE

AF:

0.102

Gnomad4 OTH

AF:

0.113

Alfa

AF:

0.0896

Hom.:

144

Bravo

AF:

0.0967

Asia WGS

AF:

0.225

AC:

779

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: reviewed by expert panel

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Hereditary antithrombin deficiency

Benign:1

Benign, reviewed by expert panel

curation

Clingen Thrombosis Variant Curation Expert Panel, ClinGen

Jul 25, 2023

The NM_000488.4:c.1154-53G>A variant is reported at a popmax FAF of 0.3028 and the highest MAF of 0.3263 (32%; 507/1554 alleles with 81 homozygotes) in the East Asian population in gnomAD v2.1.1, meeting criteria for BA1 (MAF >0.002). The variant is reported in 8 individuals with normal antithrombin levels. 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, BS2. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

6.0

DANN

Benign

0.59

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over