dbSNP rs33916072: SERPINE2:c.1072+164T>C (chr2-223980147-A-G) – 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.1072+164T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.429 in 553,892 control chromosomes in the GnomAD database, including 54,708 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 0.38 ( 12545 hom., cov: 33)

Exomes 𝑓: 0.45 ( 42163 hom. )

Consequence

SERPINE2
NM_001136528.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.242

Publications

2 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=-0.84).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.479 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001136528.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SERPINE2	NM_001136528.2	MANE Select	c.1072+164T>C	intron	N/A	NP_001130000.1	P07093-2
SERPINE2	NM_001136530.1		c.1108+164T>C	intron	N/A	NP_001130002.1	P07093-3
SERPINE2	NM_006216.4		c.1075+164T>C	intron	N/A	NP_006207.1	P07093-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SERPINE2	ENST00000409304.6	TSL:1 MANE Select	c.1072+164T>C	intron	N/A	ENSP00000386412.1	P07093-2
SERPINE2	ENST00000258405.9	TSL:1	c.1075+164T>C	intron	N/A	ENSP00000258405.4	P07093-1
SERPINE2	ENST00000409840.7	TSL:1	c.1072+164T>C	intron	N/A	ENSP00000386969.3	P07093-2

Frequencies

GnomAD3 genomes

AF:

0.381

AC:

57892

AN:

152054

Hom.:

12548

Cov.:

show subpopulations

Gnomad AFR

AF:

0.171

Gnomad AMI

AF:

0.401

Gnomad AMR

AF:

0.398

Gnomad ASJ

AF:

0.324

Gnomad EAS

AF:

0.247

Gnomad SAS

AF:

0.474

Gnomad FIN

AF:

0.561

Gnomad MID

AF:

0.307

Gnomad NFE

AF:

0.483

Gnomad OTH

AF:

0.381

GnomAD4 exome

AF:

0.447

AC:

179640

AN:

401720

Hom.:

42163

Cov.:

AF XY:

0.448

AC XY:

94481

AN XY:

210984

show subpopulations

African (AFR)

AF:

0.171

AC:

1938

AN:

11320

American (AMR)

AF:

0.406

AC:

6486

AN:

15994

Ashkenazi Jewish (ASJ)

AF:

0.328

AC:

3954

AN:

12038

East Asian (EAS)

AF:

0.242

AC:

6843

AN:

28294

South Asian (SAS)

AF:

0.471

AC:

16092

AN:

34154

European-Finnish (FIN)

AF:

0.548

AC:

19599

AN:

35766

Middle Eastern (MID)

AF:

0.352

AC:

621

AN:

1762

European-Non Finnish (NFE)

AF:

0.478

AC:

114411

AN:

239360

Other (OTH)

AF:

0.421

AC:

9696

AN:

23032

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

4443

8887

13330

17774

22217

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

600

1200

1800

2400

3000

<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:

0.381

AC:

57904

AN:

152172

Hom.:

12545

Cov.:

AF XY:

0.384

AC XY:

28554

AN XY:

74404

show subpopulations

African (AFR)

AF:

0.171

AC:

7092

AN:

41540

American (AMR)

AF:

0.398

AC:

6078

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.324

AC:

1125

AN:

3468

East Asian (EAS)

AF:

0.247

AC:

1281

AN:

5180

South Asian (SAS)

AF:

0.474

AC:

2289

AN:

4828

European-Finnish (FIN)

AF:

0.561

AC:

5928

AN:

10576

Middle Eastern (MID)

AF:

0.299

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.483

AC:

32867

AN:

67984

Other (OTH)

AF:

0.376

AC:

791

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1726

3451

5177

6902

8628

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

556

1112

1668

2224

2780

<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:

0.424

Hom.:

1807

Bravo

AF:

0.355

Asia WGS

AF:

0.340

AC:

1183

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.47

(source)

DANN

Benign

0.82

PhyloP100

-0.24

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over