dbSNP rs36034130: SERPINE2:c.487+132G>T (chr2-223997983-C-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001136528.2(SERPINE2):c.487+132G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.106 in 691,978 control chromosomes in the GnomAD database, including 4,593 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 ( 1326 hom., cov: 32)

Exomes 𝑓: 0.10 ( 3267 hom. )

Consequence

SERPINE2
NM_001136528.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.48

Publications

3 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.174 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SERPINE2	NM_001136528.2 link	c.487+132G>T		intron_variant	Intron 3 of 8	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.487+132G>T		intron_variant	Intron 3 of 8	1	NM_001136528.2	ENSP00000386412.1		P07093-2

Frequencies

GnomAD3 genomes

AF:

0.122

AC:

18559

AN:

152070

Hom.:

1321

Cov.:

show subpopulations

Gnomad AFR

AF:

0.177

Gnomad AMI

AF:

0.241

Gnomad AMR

AF:

0.127

Gnomad ASJ

AF:

0.127

Gnomad EAS

AF:

0.0231

Gnomad SAS

AF:

0.161

Gnomad FIN

AF:

0.112

Gnomad MID

AF:

0.0601

Gnomad NFE

AF:

0.0932

Gnomad OTH

AF:

0.0896

GnomAD4 exome

AF:

0.102

AC:

54996

AN:

539790

Hom.:

3267

AF XY:

0.105

AC XY:

30070

AN XY:

285748

show subpopulations

African (AFR)

AF:

0.175

AC:

2577

AN:

14748

American (AMR)

AF:

0.142

AC:

3968

AN:

27850

Ashkenazi Jewish (ASJ)

AF:

0.121

AC:

1934

AN:

15974

East Asian (EAS)

AF:

0.0189

AC:

607

AN:

32078

South Asian (SAS)

AF:

0.163

AC:

8487

AN:

52164

European-Finnish (FIN)

AF:

0.113

AC:

3946

AN:

34918

Middle Eastern (MID)

AF:

0.0810

AC:

310

AN:

3828

European-Non Finnish (NFE)

AF:

0.0921

AC:

30268

AN:

328622

Other (OTH)

AF:

0.0979

AC:

2899

AN:

29608

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

2555

5109

7664

10218

12773

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

358

716

1074

1432

1790

<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:

0.122

AC:

18597

AN:

152188

Hom.:

1326

Cov.:

AF XY:

0.123

AC XY:

9169

AN XY:

74422

show subpopulations

African (AFR)

AF:

0.177

AC:

7363

AN:

41524

American (AMR)

AF:

0.127

AC:

1944

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.127

AC:

441

AN:

3472

East Asian (EAS)

AF:

0.0235

AC:

122

AN:

5186

South Asian (SAS)

AF:

0.162

AC:

782

AN:

4824

European-Finnish (FIN)

AF:

0.112

AC:

1186

AN:

10592

Middle Eastern (MID)

AF:

0.0578

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0932

AC:

6337

AN:

67988

Other (OTH)

AF:

0.0882

AC:

186

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

815

1629

2444

3258

4073

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

204

408

612

816

1020

<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:

0.0771

Hom.:

141

Bravo

AF:

0.124

Asia WGS

AF:

0.0810

AC:

284

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

0.17

(source)

DANN

Benign

0.68

PhyloP100

-1.5

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

Computational scores

Splicing

Publications

Other links and lift over