dbSNP rs729631: SERPINE2:c.1072+109G>T (chr2-223980202-C-A) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001136528.2(SERPINE2):c.1072+109G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000221 in 887,296 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.00087 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000087 ( 0 hom. )

Consequence

SERPINE2
NM_001136528.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.252

Publications

11 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 -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BS2

High AC in GnomAd4 at 132 AD gene.

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+109G>T	intron	N/A	NP_001130000.1	P07093-2
SERPINE2	NM_001136530.1		c.1108+109G>T	intron	N/A	NP_001130002.1	P07093-3
SERPINE2	NM_006216.4		c.1075+109G>T	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+109G>T	intron	N/A	ENSP00000386412.1	P07093-2
SERPINE2	ENST00000258405.9	TSL:1	c.1075+109G>T	intron	N/A	ENSP00000258405.4	P07093-1
SERPINE2	ENST00000409840.7	TSL:1	c.1072+109G>T	intron	N/A	ENSP00000386969.3	P07093-2

Frequencies

GnomAD3 genomes

AF:

0.000861

AC:

131

AN:

152086

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00307

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000871

AC:

AN:

735092

Hom.:

Cov.:

AF XY:

0.0000752

AC XY:

AN XY:

385756

show subpopulations

African (AFR)

AF:

0.00252

AC:

AN:

19010

American (AMR)

AF:

0.000238

AC:

AN:

37804

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19164

East Asian (EAS)

AF:

0.00

AC:

AN:

33742

South Asian (SAS)

AF:

0.0000313

AC:

AN:

63824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49116

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3308

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

473356

Other (OTH)

AF:

0.000140

AC:

AN:

35768

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.000867

AC:

132

AN:

152204

Hom.:

Cov.:

AF XY:

0.000887

AC XY:

AN XY:

74420

show subpopulations

African (AFR)

AF:

0.00308

AC:

128

AN:

41512

American (AMR)

AF:

0.000261

AC:

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5172

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10594

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68016

Other (OTH)

AF:

0.00

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00

Hom.:

2360

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

2.6

(source)

DANN

Benign

0.12

PhyloP100

-0.25

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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