Variant chr18-63903295-C-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000299502.9(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
ENST00000299502.9 missense

Scores

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]

SERPINB2 links:

Genome browser will be placed here

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	Protein
SERPINB2	NM_002575.3 linkuse as main transcript	c.1238C>G	p.Ser413Cys	missense_variant	8/8	ENST00000299502.9	NP_002566.1
SERPINB2	NM_001143818.2 linkuse as main transcript	c.1238C>G	p.Ser413Cys	missense_variant	9/9		NP_001137290.1
SERPINB2	XM_024451192.2 linkuse as main transcript	c.1238C>G	p.Ser413Cys	missense_variant	8/8		XP_024306960.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SERPINB2	ENST00000299502.9 linkuse as main transcript	c.1238C>G	p.Ser413Cys	missense_variant	8/8	1	NM_002575.3	ENSP00000299502	P1
SERPINB2	ENST00000457692.5 linkuse as main transcript	c.1238C>G	p.Ser413Cys	missense_variant	9/9	5		ENSP00000401645	P1

Frequencies

GnomAD3 genomes

AF:

0.286

AC:

43471

AN:

151878

Hom.:

6811

Cov.:

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.:

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.:

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

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

LIST_S2

Benign

0.81

.;T

MetaRNN

Benign

0.00038

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.61

N;N

MutationTaster

Benign

0.97

P;P

PrimateAI

Benign

0.26

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

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over