Variant chr11-57599749-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000062.3(SERPING1):c.52-130C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.359 in 1,287,044 control chromosomes in the GnomAD database, including 89,490 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.39 ( 12531 hom., cov: 31)

Exomes 𝑓: 0.35 ( 76959 hom. )

Consequence

SERPING1
NM_000062.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.38

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 links:

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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=-0.79).

BP6

Variant 11-57599749-C-T is Benign according to our data. Variant chr11-57599749-C-T is described in ClinVar as [Benign]. Clinvar id is 983239.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-57599749-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.735 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SERPING1	NM_000062.3 linkuse as main transcript	c.52-130C>T		intron_variant		ENST00000278407.9
SERPING1	NM_001032295.2 linkuse as main transcript	c.52-130C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SERPING1	ENST00000278407.9 linkuse as main transcript	c.52-130C>T		intron_variant		1	NM_000062.3	P2	P05155-1

Frequencies

GnomAD3 genomes

AF:

0.395

AC:

59934

AN:

151838

Hom.:

12523

Cov.:

show subpopulations

Gnomad AFR

AF:

0.445

Gnomad AMI

AF:

0.555

Gnomad AMR

AF:

0.474

Gnomad ASJ

AF:

0.458

Gnomad EAS

AF:

0.755

Gnomad SAS

AF:

0.452

Gnomad FIN

AF:

0.343

Gnomad MID

AF:

0.446

Gnomad NFE

AF:

0.318

Gnomad OTH

AF:

0.387

GnomAD4 exome

AF:

0.354

AC:

401906

AN:

1135086

Hom.:

76959

AF XY:

0.356

AC XY:

206031

AN XY:

578696

show subpopulations

Gnomad4 AFR exome

AF:

0.450

Gnomad4 AMR exome

AF:

0.560

Gnomad4 ASJ exome

AF:

0.454

Gnomad4 EAS exome

AF:

0.761

Gnomad4 SAS exome

AF:

0.442

Gnomad4 FIN exome

AF:

0.330

Gnomad4 NFE exome

AF:

0.310

Gnomad4 OTH exome

AF:

0.379

GnomAD4 genome

AF:

0.395

AC:

59977

AN:

151958

Hom.:

12531

Cov.:

AF XY:

0.401

AC XY:

29778

AN XY:

74260

show subpopulations

Gnomad4 AFR

AF:

0.445

Gnomad4 AMR

AF:

0.474

Gnomad4 ASJ

AF:

0.458

Gnomad4 EAS

AF:

0.755

Gnomad4 SAS

AF:

0.453

Gnomad4 FIN

AF:

0.343

Gnomad4 NFE

AF:

0.318

Gnomad4 OTH

AF:

0.387

Alfa

AF:

0.348

Hom.:

10126

Bravo

AF:

0.411

Asia WGS

AF:

0.578

AC:

2008

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

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

Hereditary angioedema type 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

CeMIA

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). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

8.4

DANN

Benign

0.52

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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