Genetic Variant NM_001136528.2:c.487+11G>A (chr2-223998104-C-T) – 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+11G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.216 in 1,594,248 control chromosomes in the GnomAD database, including 42,789 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 0.29 ( 8287 hom., cov: 32)

Exomes 𝑓: 0.21 ( 34502 hom. )

Consequence

SERPINE2
NM_001136528.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.24

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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.528 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SERPINE2	NM_001136528.2 link	c.487+11G>A		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+11G>A		intron_variant	Intron 3 of 8	1	NM_001136528.2	ENSP00000386412.1		P07093-2

Frequencies

GnomAD3 genomes

AF:

0.291

AC:

44175

AN:

151972

Hom.:

8267

Cov.:

show subpopulations

Gnomad AFR

AF:

0.534

Gnomad AMI

AF:

0.222

Gnomad AMR

AF:

0.234

Gnomad ASJ

AF:

0.276

Gnomad EAS

AF:

0.139

Gnomad SAS

AF:

0.171

Gnomad FIN

AF:

0.111

Gnomad MID

AF:

0.326

Gnomad NFE

AF:

0.205

Gnomad OTH

AF:

0.303

GnomAD2 exomes

AF:

0.208

AC:

51987

AN:

250398

AF XY:

0.205

show subpopulations

Gnomad AFR exome

AF:

0.535

Gnomad AMR exome

AF:

0.157

Gnomad ASJ exome

AF:

0.274

Gnomad EAS exome

AF:

0.134

Gnomad FIN exome

AF:

0.113

Gnomad NFE exome

AF:

0.210

Gnomad OTH exome

AF:

0.214

GnomAD4 exome

AF:

0.208

AC:

300545

AN:

1442158

Hom.:

34502

Cov.:

AF XY:

0.208

AC XY:

149366

AN XY:

718688

show subpopulations

African (AFR)

AF:

0.543

AC:

17871

AN:

32926

American (AMR)

AF:

0.165

AC:

7386

AN:

44638

Ashkenazi Jewish (ASJ)

AF:

0.275

AC:

7139

AN:

25996

East Asian (EAS)

AF:

0.156

AC:

6189

AN:

39616

South Asian (SAS)

AF:

0.177

AC:

15184

AN:

85824

European-Finnish (FIN)

AF:

0.115

AC:

6134

AN:

53324

Middle Eastern (MID)

AF:

0.329

AC:

1885

AN:

5730

European-Non Finnish (NFE)

AF:

0.206

AC:

225038

AN:

1094376

Other (OTH)

AF:

0.230

AC:

13719

AN:

59728

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

10939

21877

32816

43754

54693

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7816

15632

23448

31264

39080

<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:

0.291

AC:

44232

AN:

152090

Hom.:

8287

Cov.:

AF XY:

0.285

AC XY:

21198

AN XY:

74344

show subpopulations

African (AFR)

AF:

0.534

AC:

22155

AN:

41466

American (AMR)

AF:

0.234

AC:

3573

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.276

AC:

958

AN:

3472

East Asian (EAS)

AF:

0.140

AC:

721

AN:

5168

South Asian (SAS)

AF:

0.170

AC:

817

AN:

4810

European-Finnish (FIN)

AF:

0.111

AC:

1180

AN:

10590

Middle Eastern (MID)

AF:

0.306

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.205

AC:

13904

AN:

67988

Other (OTH)

AF:

0.299

AC:

632

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1466

2931

4397

5862

7328

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

416

832

1248

1664

2080

<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:

0.280

Hom.:

1769

Bravo

AF:

0.313

Asia WGS

AF:

0.145

AC:

502

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.0030

(source)

DANN

Benign

0.54

PhyloP100

-2.2

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