Genetic Variant SERPINE2:p.Leu77Leu (chr2-224001670-G-A) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_001136528.2(SERPINE2):c.231C>T(p.Leu77Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.119 in 1,613,844 control chromosomes in the GnomAD database, including 13,259 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 0.15 ( 2006 hom., cov: 32)

Exomes 𝑓: 0.12 ( 11253 hom. )

Consequence

SERPINE2
NM_001136528.2 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.11

Publications

16 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 -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.56).

BP7

Synonymous conserved (PhyloP=1.11 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.224 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SERPINE2	NM_001136528.2 link	c.231C>T	p.Leu77Leu	synonymous_variant	Exon 2 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.231C>T	p.Leu77Leu	synonymous_variant	Exon 2 of 9	1	NM_001136528.2	ENSP00000386412.1		P07093-2

Frequencies

GnomAD3 genomes

AF:

0.151

AC:

22937

AN:

152060

Hom.:

1997

Cov.:

show subpopulations

Gnomad AFR

AF:

0.217

Gnomad AMI

AF:

0.241

Gnomad AMR

AF:

0.156

Gnomad ASJ

AF:

0.148

Gnomad EAS

AF:

0.234

Gnomad SAS

AF:

0.212

Gnomad FIN

AF:

0.125

Gnomad MID

AF:

0.0823

Gnomad NFE

AF:

0.103

Gnomad OTH

AF:

0.121

GnomAD2 exomes

AF:

0.148

AC:

37047

AN:

250882

AF XY:

0.146

show subpopulations

Gnomad AFR exome

AF:

0.218

Gnomad AMR exome

AF:

0.193

Gnomad ASJ exome

AF:

0.146

Gnomad EAS exome

AF:

0.229

Gnomad FIN exome

AF:

0.126

Gnomad NFE exome

AF:

0.0998

Gnomad OTH exome

AF:

0.130

GnomAD4 exome

AF:

0.116

AC:

169562

AN:

1461666

Hom.:

11253

Cov.:

AF XY:

0.119

AC XY:

86234

AN XY:

727142

show subpopulations

African (AFR)

AF:

0.222

AC:

7425

AN:

33478

American (AMR)

AF:

0.187

AC:

8379

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.144

AC:

3754

AN:

26134

East Asian (EAS)

AF:

0.219

AC:

8694

AN:

39698

South Asian (SAS)

AF:

0.207

AC:

17888

AN:

86250

European-Finnish (FIN)

AF:

0.127

AC:

6753

AN:

53264

Middle Eastern (MID)

AF:

0.117

AC:

676

AN:

5762

European-Non Finnish (NFE)

AF:

0.0975

AC:

108459

AN:

1111964

Other (OTH)

AF:

0.125

AC:

7534

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

7803

15607

23410

31214

39017

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4198

8396

12594

16792

20990

<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:

0.151

AC:

22987

AN:

152178

Hom.:

2006

Cov.:

AF XY:

0.153

AC XY:

11407

AN XY:

74394

show subpopulations

African (AFR)

AF:

0.217

AC:

8998

AN:

41508

American (AMR)

AF:

0.157

AC:

2402

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.148

AC:

514

AN:

3470

East Asian (EAS)

AF:

0.235

AC:

1212

AN:

5160

South Asian (SAS)

AF:

0.213

AC:

1028

AN:

4828

European-Finnish (FIN)

AF:

0.125

AC:

1326

AN:

10610

Middle Eastern (MID)

AF:

0.0850

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.103

AC:

7009

AN:

67992

Other (OTH)

AF:

0.120

AC:

254

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

983

1966

2949

3932

4915

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

252

504

756

1008

1260

<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:

0.117

Hom.:

1637

Bravo

AF:

0.155

Asia WGS

AF:

0.195

AC:

678

AN:

3478

EpiCase

AF:

0.0976

EpiControl

AF:

0.0990

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.56

CADD

Benign

6.4

(source)

DANN

Benign

0.49

PhyloP100

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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

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