rs7588220

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_001136528.2(SERPINE2):​c.-22-6965C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0158 in 152,248 control chromosomes in the GnomAD database, including 35 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 0.016 ( 35 hom., cov: 33)

Consequence

SERPINE2
NM_001136528.2 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.16

Publications

1 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]

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=-0.9).
BS1
Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0158 (2411/152248) while in subpopulation NFE AF = 0.0248 (1685/68020). AF 95% confidence interval is 0.0238. There are 35 homozygotes in GnomAd4. There are 1137 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
BS2
High AC in GnomAd4 at 2411 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

Selected
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
SERPINE2
NM_001136528.2
MANE Select
c.-22-6965C>T
intron
N/ANP_001130000.1
SERPINE2
NM_001136530.1
c.15-6965C>T
intron
N/ANP_001130002.1
SERPINE2
NM_006216.4
c.-22-6965C>T
intron
N/ANP_006207.1

Ensembl Transcripts

Selected
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
SERPINE2
ENST00000409304.6
TSL:1 MANE Select
c.-22-6965C>T
intron
N/AENSP00000386412.1
SERPINE2
ENST00000258405.9
TSL:1
c.-22-6965C>T
intron
N/AENSP00000258405.4
SERPINE2
ENST00000409840.7
TSL:1
c.-22-6965C>T
intron
N/AENSP00000386969.3

Frequencies

GnomAD3 genomes
AF:
0.0158
AC:
2411
AN:
152130
Hom.:
35
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00430
Gnomad AMI
AF:
0.105
Gnomad AMR
AF:
0.0105
Gnomad ASJ
AF:
0.00634
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00663
Gnomad FIN
AF:
0.0166
Gnomad MID
AF:
0.0158
Gnomad NFE
AF:
0.0248
Gnomad OTH
AF:
0.0268
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.0158
AC:
2411
AN:
152248
Hom.:
35
Cov.:
33
AF XY:
0.0153
AC XY:
1137
AN XY:
74430
show subpopulations
African (AFR)
AF:
0.00428
AC:
178
AN:
41542
American (AMR)
AF:
0.0105
AC:
161
AN:
15292
Ashkenazi Jewish (ASJ)
AF:
0.00634
AC:
22
AN:
3472
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5182
South Asian (SAS)
AF:
0.00663
AC:
32
AN:
4826
European-Finnish (FIN)
AF:
0.0166
AC:
176
AN:
10598
Middle Eastern (MID)
AF:
0.0170
AC:
5
AN:
294
European-Non Finnish (NFE)
AF:
0.0248
AC:
1685
AN:
68020
Other (OTH)
AF:
0.0265
AC:
56
AN:
2110
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.505
Heterozygous variant carriers
0
129
257
386
514
643
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
28
56
84
112
140
<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:
0.0233
Hom.:
71
Bravo
AF:
0.0159
Asia WGS
AF:
0.00260
AC:
9
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.90
CADD
Benign
1.1
DANN
Benign
0.58
PhyloP100
-1.2
Mutation Taster
=100/0
polymorphism

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

Other links and lift over

dbSNP: rs7588220; hg19: chr2-224873604; API