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GeneBe

18-63903295-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002575.3(SERPINB2):c.1238C>G(p.Ser413Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.242 in 1,526,154 control chromosomes in the GnomAD database, including 47,860 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.29 ( 6832 hom., cov: 32)
Exomes 𝑓: 0.24 ( 41028 hom. )

Consequence

SERPINB2
NM_002575.3 missense

Scores

17

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.933
Variant links:
Genes affected
SERPINB2 (HGNC:8584): (serpin family B member 2) Predicted to enable serine-type endopeptidase inhibitor activity. Predicted to be involved in negative regulation of endopeptidase activity. Predicted to be located in extracellular region and plasma membrane. Predicted to be active in extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=3.8471818E-4).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.462 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SERPINB2NM_002575.3 linkuse as main transcriptc.1238C>G p.Ser413Cys missense_variant 8/8 ENST00000299502.9
SERPINB2NM_001143818.2 linkuse as main transcriptc.1238C>G p.Ser413Cys missense_variant 9/9
SERPINB2XM_024451192.2 linkuse as main transcriptc.1238C>G p.Ser413Cys missense_variant 8/8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SERPINB2ENST00000299502.9 linkuse as main transcriptc.1238C>G p.Ser413Cys missense_variant 8/81 NM_002575.3 P1
SERPINB2ENST00000457692.5 linkuse as main transcriptc.1238C>G p.Ser413Cys missense_variant 9/95 P1

Frequencies

GnomAD3 genomes
AF:
0.286
AC:
43471
AN:
151878
Hom.:
6811
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.363
Gnomad AMI
AF:
0.124
Gnomad AMR
AF:
0.370
Gnomad ASJ
AF:
0.184
Gnomad EAS
AF:
0.478
Gnomad SAS
AF:
0.296
Gnomad FIN
AF:
0.233
Gnomad MID
AF:
0.354
Gnomad NFE
AF:
0.220
Gnomad OTH
AF:
0.304
GnomAD3 exomes
AF:
0.289
AC:
53535
AN:
185116
Hom.:
8685
AF XY:
0.282
AC XY:
27572
AN XY:
97716
show subpopulations
Gnomad AFR exome
AF:
0.370
Gnomad AMR exome
AF:
0.435
Gnomad ASJ exome
AF:
0.200
Gnomad EAS exome
AF:
0.470
Gnomad SAS exome
AF:
0.295
Gnomad FIN exome
AF:
0.235
Gnomad NFE exome
AF:
0.220
Gnomad OTH exome
AF:
0.277
GnomAD4 exome
AF:
0.237
AC:
326206
AN:
1374158
Hom.:
41028
Cov.:
32
AF XY:
0.238
AC XY:
160668
AN XY:
674504
show subpopulations
Gnomad4 AFR exome
AF:
0.369
Gnomad4 AMR exome
AF:
0.416
Gnomad4 ASJ exome
AF:
0.186
Gnomad4 EAS exome
AF:
0.404
Gnomad4 SAS exome
AF:
0.281
Gnomad4 FIN exome
AF:
0.228
Gnomad4 NFE exome
AF:
0.219
Gnomad4 OTH exome
AF:
0.259
GnomAD4 genome
AF:
0.286
AC:
43527
AN:
151996
Hom.:
6832
Cov.:
32
AF XY:
0.289
AC XY:
21504
AN XY:
74282
show subpopulations
Gnomad4 AFR
AF:
0.363
Gnomad4 AMR
AF:
0.371
Gnomad4 ASJ
AF:
0.184
Gnomad4 EAS
AF:
0.477
Gnomad4 SAS
AF:
0.296
Gnomad4 FIN
AF:
0.233
Gnomad4 NFE
AF:
0.220
Gnomad4 OTH
AF:
0.310
Alfa
AF:
0.216
Hom.:
2480
Bravo
AF:
0.302
TwinsUK
AF:
0.202
AC:
749
ALSPAC
AF:
0.209
AC:
804
ESP6500AA
AF:
0.369
AC:
1624
ESP6500EA
AF:
0.217
AC:
1869
ExAC
AF:
0.273
AC:
32773
Asia WGS
AF:
0.389
AC:
1349
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.077
BayesDel_addAF
Benign
-0.61
T
BayesDel_noAF
Benign
-0.51
Cadd
Benign
1.5
Dann
Benign
0.44
DEOGEN2
Benign
0.12
T;T
Eigen
Benign
-1.1
Eigen_PC
Benign
-1.0
FATHMM_MKL
Benign
0.22
N
MetaRNN
Benign
0.00038
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.61
N;N
MutationTaster
Benign
0.97
P;P
PrimateAI
Benign
0.26
T
PROVEAN
Benign
3.3
N;N
REVEL
Benign
0.12
Sift
Benign
1.0
T;T
Sift4G
Benign
1.0
T;T
Polyphen
0.0030
B;B
Vest4
0.065
MPC
0.016
ClinPred
0.00070
T
GERP RS
1.3
Varity_R
0.19
gMVP
0.19

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs6104; hg19: chr18-61570529; COSMIC: COSV53073025; COSMIC: COSV53073025; API