rs2511988

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000062.3(SERPING1):c.1030-20A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.653 in 1,607,436 control chromosomes in the GnomAD database, including 350,180 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.60 ( 28314 hom., cov: 32)

Exomes 𝑓: 0.66 ( 321866 hom. )

Consequence

SERPING1
NM_000062.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: 1.10

Publications

24 publications found

Variant links:

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]

SERPING1 Gene-Disease associations (from GenCC):

hereditary angioedema with C1Inh deficiency
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Labcorp Genetics (formerly Invitae)
C1 inhibitor deficiency
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
hereditary angioedema type 1
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
hereditary angioedema type 2
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

SERPING1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BP6

Variant 11-57611697-A-G is Benign according to our data. Variant chr11-57611697-A-G is described in ClinVar as Benign. ClinVar VariationId is 254785.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.684 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SERPING1	NM_000062.3 link	c.1030-20A>G		intron_variant	Intron 6 of 7	ENST00000278407.9	NP_000053.2	P05155-1E9KL26
SERPING1	NM_001032295.2 link	c.1030-20A>G		intron_variant	Intron 5 of 6		NP_001027466.1	P05155-1E9KL26

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SERPING1	ENST00000278407.9 link	c.1030-20A>G		intron_variant	Intron 6 of 7	1	NM_000062.3	ENSP00000278407.4		P05155-1

Frequencies

GnomAD3 genomes

AF:

0.601

AC:

91352

AN:

151918

Hom.:

28299

Cov.:

show subpopulations

Gnomad AFR

AF:

0.525

Gnomad AMI

AF:

0.466

Gnomad AMR

AF:

0.525

Gnomad ASJ

AF:

0.543

Gnomad EAS

AF:

0.250

Gnomad SAS

AF:

0.549

Gnomad FIN

AF:

0.674

Gnomad MID

AF:

0.551

Gnomad NFE

AF:

0.689

Gnomad OTH

AF:

0.608

GnomAD2 exomes

AF:

0.581

AC:

145574

AN:

250716

AF XY:

0.590

show subpopulations

Gnomad AFR exome

AF:

0.518

Gnomad AMR exome

AF:

0.426

Gnomad ASJ exome

AF:

0.551

Gnomad EAS exome

AF:

0.247

Gnomad FIN exome

AF:

0.679

Gnomad NFE exome

AF:

0.679

Gnomad OTH exome

AF:

0.610

GnomAD4 exome

AF:

0.658

AC:

957618

AN:

1455400

Hom.:

321866

Cov.:

AF XY:

0.656

AC XY:

475249

AN XY:

724554

show subpopulations

African (AFR)

AF:

0.515

AC:

17140

AN:

33308

American (AMR)

AF:

0.438

AC:

19580

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.546

AC:

14229

AN:

26080

East Asian (EAS)

AF:

0.242

AC:

9583

AN:

39654

South Asian (SAS)

AF:

0.562

AC:

48356

AN:

86088

European-Finnish (FIN)

AF:

0.683

AC:

36428

AN:

53370

Middle Eastern (MID)

AF:

0.601

AC:

3434

AN:

5718

European-Non Finnish (NFE)

AF:

0.697

AC:

771144

AN:

1106296

Other (OTH)

AF:

0.627

AC:

37724

AN:

60172

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

16920

33840

50761

67681

84601

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

19304

38608

57912

77216

96520

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.601

AC:

91407

AN:

152036

Hom.:

28314

Cov.:

AF XY:

0.596

AC XY:

44258

AN XY:

74308

show subpopulations

African (AFR)

AF:

0.525

AC:

21738

AN:

41436

American (AMR)

AF:

0.525

AC:

8015

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.543

AC:

1886

AN:

3472

East Asian (EAS)

AF:

0.251

AC:

1297

AN:

5168

South Asian (SAS)

AF:

0.548

AC:

2636

AN:

4808

European-Finnish (FIN)

AF:

0.674

AC:

7135

AN:

10580

Middle Eastern (MID)

AF:

0.544

AC:

160

AN:

294

European-Non Finnish (NFE)

AF:

0.689

AC:

46835

AN:

67982

Other (OTH)

AF:

0.608

AC:

1281

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1814

3628

5443

7257

9071

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

758

1516

2274

3032

3790

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.630

Hom.:

19410

Bravo

AF:

0.582

Asia WGS

AF:

0.417

AC:

1451

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Hereditary angioedema type 1

Benign:4

Oct 09, 2014

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

CeMIA

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium (BA1), allele frequency is greater than expected for disorder (BS1), it is observed in a healthy adult individual (BS2), it is predicted to be benign by multiple in silico algorithms (BP4), it is found in a case with an alternate molecular basis for the disease (BP5) and/or reputable source recently reports variant as benign (BP6). -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Jul 15, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:3

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 19200915, 18842294) -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

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:2

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

7.6

(source)

DANN

Benign

0.56

PhyloP100

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over