Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The ENST00000278407.9(SERPING1):c.279G>A(p.Glu93Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000072 in 1,611,142 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.000086 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000071 ( 1 hom. )

Consequence

SERPING1
ENST00000278407.9 synonymous

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.565

Publications

0 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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 11-57600106-G-A is Benign according to our data. Variant chr11-57600106-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 403429.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.565 with no splicing effect.

BS1

Variant frequency is greater than expected in population mid. GnomAdExome4 allele frequency = 0.0000706 (103/1459782) while in subpopulation MID AF = 0.0052 (30/5764). AF 95% confidence interval is 0.00375. There are 1 homozygotes in GnomAdExome4. There are 45 alleles in the male GnomAdExome4 subpopulation. Median coverage is 34. This position passed quality control check.

BS2

High AC in GnomAd4 at 13 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000278407.9. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SERPING1	NM_000062.3	MANE Select	c.279G>A	p.Glu93Glu	synonymous	Exon 3 of 8	NP_000053.2
	SERPING1	NM_001032295.2		c.279G>A	p.Glu93Glu	synonymous	Exon 2 of 7	NP_001027466.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
SERPING1	ENST00000278407.9	TSL:1 MANE Select	c.279G>A	p.Glu93Glu	synonymous	Exon 3 of 8	ENSP00000278407.4
SERPING1	ENST00000619430.2	TSL:1	c.279G>A	p.Glu93Glu	synonymous	Exon 3 of 7	ENSP00000478572.2
SERPING1	ENST00000531133.5	TSL:1	n.51+1785G>A		intron	N/A	ENSP00000435431.1

Frequencies

GnomAD3 genomes

AF:

0.0000860

AC:

AN:

151244

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00116

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0000737

Gnomad OTH

AF:

0.000481

GnomAD2 exomes

AF:

0.0000841

AC:

AN:

249638

AF XY:

0.0000741

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000874

Gnomad ASJ exome

AF:

0.000997

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000622

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.0000706

AC:

103

AN:

1459782

Hom.:

Cov.:

AF XY:

0.0000620

AC XY:

AN XY:

726272

show subpopulations

African (AFR)

AF:

0.0000598

AC:

AN:

33428

American (AMR)

AF:

0.0000672

AC:

AN:

44644

Ashkenazi Jewish (ASJ)

AF:

0.00119

AC:

AN:

26122

East Asian (EAS)

AF:

0.00

AC:

AN:

39682

South Asian (SAS)

AF:

0.00

AC:

AN:

86202

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53396

Middle Eastern (MID)

AF:

0.00520

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.0000162

AC:

AN:

1110244

Other (OTH)

AF:

0.000315

AC:

AN:

60300

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.0000859

AC:

AN:

151360

Hom.:

Cov.:

AF XY:

0.0000676

AC XY:

AN XY:

73936

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41178

American (AMR)

AF:

0.00

AC:

AN:

15186

Ashkenazi Jewish (ASJ)

AF:

0.00116

AC:

AN:

3456

East Asian (EAS)

AF:

0.00

AC:

AN:

5144

South Asian (SAS)

AF:

0.00

AC:

AN:

4768

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10464

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000737

AC:

AN:

67864

Other (OTH)

AF:

0.000476

AC:

AN:

2100

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.548

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000203

Hom.:

Bravo

AF:

0.0000604

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

ClinVar submissions as Germline

Significance:Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Inborn genetic diseases (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.61

(source)

DANN

Benign

0.33

PhyloP100

-0.56

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

rs778803626

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over