chr1-173909694-T-C

Variant names:

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BS2_SupportingBP7BA1BP4

This summary comes from the ClinGen Evidence Repository: The variant is reported at a popmax FAF of 0.7651 and the highest MAF of 0.7792 (78%; 19440/24948 alleles with 7592 homozygotes) in the African/African-American population in gnomAD v2.1.1, meeting criteria for BA1 (MAF >0.002). The variant is reported in 1 individual with normal antithrombin levels. SpliceAI and VarSeak predict no impact on splicing and PhyloP gives a conservation score of 0.028 (<0.1). 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_Supporting, BP4, BP7. LINK:https://erepo.genome.network/evrepo/ui/classification/CA1251296/MONDO:0013144/084

Frequency

Genomes: 𝑓 0.48 ( 20306 hom., cov: 33)

Exomes 𝑓: 0.36 ( 100658 hom. )

Consequence

SERPINC1
NM_000488.4 synonymous

Scores

Clinical Significance

Benign reviewed by expert panel B:7

Conservation

PhyloP100: 0.121

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 -11 ACMG points.

BP4

For more information check the summary or visit ClinGen Evidence Repository.

BP7

For more information check the summary or visit ClinGen Evidence Repository.

BS2

For more information check the summary or visit ClinGen Evidence Repository.

BA1

For more information check the summary or visit ClinGen Evidence Repository.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SERPINC1	NM_000488.4 link	c.1011A>G	p.Gln337Gln	synonymous_variant	Exon 5 of 7	ENST00000367698.4	NP_000479.1	P01008A0A024R944

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SERPINC1	ENST00000367698.4 link	c.1011A>G	p.Gln337Gln	synonymous_variant	Exon 5 of 7	1	NM_000488.4	ENSP00000356671.3		P01008
SERPINC1	ENST00000487183.1 link	n.*36A>G		downstream_gene_variant		2

Frequencies

GnomAD3 genomes

AF:

0.476

AC:

72441

AN:

152116

Hom.:

20255

Cov.:

show subpopulations

Gnomad AFR

AF:

0.772

Gnomad AMI

AF:

0.323

Gnomad AMR

AF:

0.378

Gnomad ASJ

AF:

0.541

Gnomad EAS

AF:

0.613

Gnomad SAS

AF:

0.385

Gnomad FIN

AF:

0.293

Gnomad MID

AF:

0.535

Gnomad NFE

AF:

0.341

Gnomad OTH

AF:

0.464

GnomAD3 exomes

AF:

0.394

AC:

99142

AN:

251340

Hom.:

22179

AF XY:

0.391

AC XY:

53095

AN XY:

135834

show subpopulations

Gnomad AFR exome

AF:

0.785

Gnomad AMR exome

AF:

0.274

Gnomad ASJ exome

AF:

0.535

Gnomad EAS exome

AF:

0.647

Gnomad SAS exome

AF:

0.379

Gnomad FIN exome

AF:

0.296

Gnomad NFE exome

AF:

0.345

Gnomad OTH exome

AF:

0.398

GnomAD4 exome

AF:

0.360

AC:

526270

AN:

1461450

Hom.:

100658

Cov.:

AF XY:

0.360

AC XY:

262001

AN XY:

727022

show subpopulations

Gnomad4 AFR exome

AF:

0.792

Gnomad4 AMR exome

AF:

0.282

Gnomad4 ASJ exome

AF:

0.536

Gnomad4 EAS exome

AF:

0.577

Gnomad4 SAS exome

AF:

0.382

Gnomad4 FIN exome

AF:

0.300

Gnomad4 NFE exome

AF:

0.336

Gnomad4 OTH exome

AF:

0.405

GnomAD4 genome

AF:

0.477

AC:

72555

AN:

152234

Hom.:

20306

Cov.:

AF XY:

0.472

AC XY:

35120

AN XY:

74434

show subpopulations

Gnomad4 AFR

AF:

0.773

Gnomad4 AMR

AF:

0.378

Gnomad4 ASJ

AF:

0.541

Gnomad4 EAS

AF:

0.613

Gnomad4 SAS

AF:

0.384

Gnomad4 FIN

AF:

0.293

Gnomad4 NFE

AF:

0.341

Gnomad4 OTH

AF:

0.464

Alfa

AF:

0.387

Hom.:

16513

Bravo

AF:

0.497

Asia WGS

AF:

0.515

AC:

1793

AN:

3478

EpiCase

AF:

0.367

EpiControl

AF:

0.367

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: reviewed by expert panel

LINK: link

Submissions by phenotype

Hereditary antithrombin deficiency

Benign:4

Jul 15, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jul 25, 2023

Clingen Thrombosis Variant Curation Expert Panel, ClinGen

Significance: Benign

Review Status: reviewed by expert panel

Collection Method: curation

The variant is reported at a popmax FAF of 0.7651 and the highest MAF of 0.7792 (78%; 19440/24948 alleles with 7592 homozygotes) in the African/African-American population in gnomAD v2.1.1, meeting criteria for BA1 (MAF >0.002). The variant is reported in 1 individual with normal antithrombin levels. SpliceAI and VarSeak predict no impact on splicing and PhyloP gives a conservation score of 0.028 (<0.1). 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_Supporting, BP4, BP7. -

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:2

Oct 31, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.60

CADD

Benign

9.6

DANN

Benign

0.56

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

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