dbSNP rs6712954: SERPINE2:p.Asn185Asn (chr2-223991933-G-A) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_ModerateBP7BA1

The NM_001136528.2(SERPINE2):c.555C>T(p.Asn185Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0737 in 1,613,120 control chromosomes in the GnomAD database, including 7,155 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.12 ( 1521 hom., cov: 32)

Exomes 𝑓: 0.069 ( 5634 hom. )

Consequence

SERPINE2
NM_001136528.2 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0740

Publications

19 publications found

Variant links:

Genes affected

SERPINE2 (HGNC:8951): (serpin family E member 2) This gene encodes a member of the serpin family of proteins, a group of proteins that inhibit serine proteases. Thrombin, urokinase, plasmin and trypsin are among the proteases that this family member can inhibit. This gene is a susceptibility gene for chronic obstructive pulmonary disease and for emphysema. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2012]

SERPINE2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.43).

BP7

Synonymous conserved (PhyloP=0.074 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.214 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SERPINE2	NM_001136528.2 link	c.555C>T	p.Asn185Asn	synonymous_variant	Exon 4 of 9	ENST00000409304.6	NP_001130000.1	P07093-2A0A024R498

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SERPINE2	ENST00000409304.6 link	c.555C>T	p.Asn185Asn	synonymous_variant	Exon 4 of 9	1	NM_001136528.2	ENSP00000386412.1		P07093-2

Frequencies

GnomAD3 genomes

AF:

0.117

AC:

17833

AN:

152094

Hom.:

1517

Cov.:

show subpopulations

Gnomad AFR

AF:

0.207

Gnomad AMI

AF:

0.0208

Gnomad AMR

AF:

0.220

Gnomad ASJ

AF:

0.143

Gnomad EAS

AF:

0.161

Gnomad SAS

AF:

0.0626

Gnomad FIN

AF:

0.0120

Gnomad MID

AF:

0.168

Gnomad NFE

AF:

0.0554

Gnomad OTH

AF:

0.139

GnomAD2 exomes

AF:

0.107

AC:

26810

AN:

250094

AF XY:

0.0962

show subpopulations

Gnomad AFR exome

AF:

0.205

Gnomad AMR exome

AF:

0.293

Gnomad ASJ exome

AF:

0.138

Gnomad EAS exome

AF:

0.169

Gnomad FIN exome

AF:

0.0145

Gnomad NFE exome

AF:

0.0566

Gnomad OTH exome

AF:

0.102

GnomAD4 exome

AF:

0.0692

AC:

101100

AN:

1460908

Hom.:

5634

Cov.:

AF XY:

0.0679

AC XY:

49371

AN XY:

726738

show subpopulations

African (AFR)

AF:

0.209

AC:

6986

AN:

33412

American (AMR)

AF:

0.282

AC:

12557

AN:

44526

Ashkenazi Jewish (ASJ)

AF:

0.142

AC:

3696

AN:

26050

East Asian (EAS)

AF:

0.156

AC:

6186

AN:

39684

South Asian (SAS)

AF:

0.0565

AC:

4862

AN:

86122

European-Finnish (FIN)

AF:

0.0163

AC:

871

AN:

53390

Middle Eastern (MID)

AF:

0.166

AC:

959

AN:

5760

European-Non Finnish (NFE)

AF:

0.0538

AC:

59790

AN:

1111598

Other (OTH)

AF:

0.0860

AC:

5193

AN:

60366

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

4649

9298

13946

18595

23244

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.117

AC:

17859

AN:

152212

Hom.:

1521

Cov.:

AF XY:

0.118

AC XY:

8759

AN XY:

74416

show subpopulations

African (AFR)

AF:

0.207

AC:

8597

AN:

41492

American (AMR)

AF:

0.221

AC:

3375

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.143

AC:

495

AN:

3470

East Asian (EAS)

AF:

0.161

AC:

832

AN:

5174

South Asian (SAS)

AF:

0.0628

AC:

303

AN:

4824

European-Finnish (FIN)

AF:

0.0120

AC:

127

AN:

10616

Middle Eastern (MID)

AF:

0.167

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0554

AC:

3771

AN:

68018

Other (OTH)

AF:

0.138

AC:

291

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

738

1475

2213

2950

3688

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.100

Hom.:

1961

Bravo

AF:

0.139

Asia WGS

AF:

0.0940

AC:

326

AN:

3478

EpiCase

AF:

0.0679

EpiControl

AF:

0.0680

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.43

CADD

Benign

2.4

(source)

DANN

Benign

0.78

PhyloP100

0.074

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=97/3

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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.

rs6712954

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over