dbSNP rs6098: SERPINB2:p.Asn120Asp (chr18-63897160-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_002575.3(SERPINB2):c.358A>G(p.Asn120Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.244 in 1,611,998 control chromosomes in the GnomAD database, including 51,138 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 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 the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.29 ( 6841 hom., cov: 32)

Exomes 𝑓: 0.24 ( 44297 hom. )

Consequence

SERPINB2
NM_002575.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.809

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:

ENSG00000289724 (HGNC:):

ENSG00000289724 links:

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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=0.001850158).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.463 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SERPINB2	NM_002575.3 link	c.358A>G	p.Asn120Asp	missense_variant	Exon 4 of 8	ENST00000299502.9	NP_002566.1	P05120
SERPINB2	NM_001143818.2 link	c.358A>G	p.Asn120Asp	missense_variant	Exon 5 of 9		NP_001137290.1	P05120
SERPINB2	XM_024451192.2 link	c.358A>G	p.Asn120Asp	missense_variant	Exon 4 of 8		XP_024306960.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SERPINB2	ENST00000299502.9 link	c.358A>G	p.Asn120Asp	missense_variant	Exon 4 of 8	1	NM_002575.3	ENSP00000299502.4		P05120
ENSG00000289724	ENST00000397996.6 link	c.-15A>G		upstream_gene_variant		5		ENSP00000381082.2		H7BYS2

Frequencies

GnomAD3 genomes

AF:

0.286

AC:

43494

AN:

151964

Hom.:

6820

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:

0.479

Gnomad SAS

AF:

0.297

Gnomad FIN

AF:

0.233

Gnomad MID

AF:

0.358

Gnomad NFE

AF:

0.220

Gnomad OTH

AF:

0.304

GnomAD3 exomes

AF:

0.284

AC:

71089

AN:

250042

Hom.:

11396

AF XY:

0.276

AC XY:

37288

AN XY:

135198

show subpopulations

Gnomad AFR exome

AF:

0.368

Gnomad AMR exome

AF:

0.425

Gnomad ASJ exome

AF:

0.189

Gnomad EAS exome

AF:

0.471

Gnomad SAS exome

AF:

0.281

Gnomad FIN exome

AF:

0.233

Gnomad NFE exome

AF:

0.220

Gnomad OTH exome

AF:

0.267

GnomAD4 exome

AF:

0.239

AC:

349163

AN:

1459916

Hom.:

44297

Cov.:

AF XY:

0.240

AC XY:

173944

AN XY:

726276

show subpopulations

Gnomad4 AFR exome

AF:

0.370

Gnomad4 AMR exome

AF:

0.414

Gnomad4 ASJ exome

AF:

0.186

Gnomad4 EAS exome

AF:

0.404

Gnomad4 SAS exome

AF:

0.279

Gnomad4 FIN exome

AF:

0.228

Gnomad4 NFE exome

AF:

0.220

Gnomad4 OTH exome

AF:

0.260

GnomAD4 genome

AF:

0.286

AC:

43550

AN:

152082

Hom.:

6841

Cov.:

AF XY:

0.290

AC XY:

21525

AN XY:

74326

show subpopulations

Gnomad4 AFR

AF:

0.363

Gnomad4 AMR

AF:

0.370

Gnomad4 ASJ

AF:

0.184

Gnomad4 EAS

AF:

0.479

Gnomad4 SAS

AF:

0.297

Gnomad4 FIN

AF:

0.233

Gnomad4 NFE

AF:

0.220

Gnomad4 OTH

AF:

0.310

Alfa

AF:

0.233

Hom.:

8462

Bravo

AF:

0.302

TwinsUK

AF:

0.202

AC:

748

ALSPAC

AF:

0.208

AC:

803

ESP6500AA

AF:

0.369

AC:

1626

ESP6500EA

AF:

0.218

AC:

1878

ExAC

AF:

0.279

AC:

33823

Asia WGS

AF:

0.389

AC:

1350

AN:

3478

EpiCase

AF:

0.229

EpiControl

AF:

0.224

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.055

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Benign

0.83

DEOGEN2

Benign

0.10

T;T;T;T

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.84

FATHMM_MKL

Benign

0.017

LIST_S2

Benign

0.028

.;T;T;T

MetaRNN

Benign

0.0019

T;T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

-1.4

N;N;.;.

PrimateAI

Benign

0.26

PROVEAN

Benign

-0.060

N;N;N;N

REVEL

Benign

0.14

Sift

Benign

0.80

T;T;T;T

Sift4G

Benign

0.67

T;T;T;T

Polyphen

0.0

B;B;.;.

Vest4

0.017

MPC

0.016

ClinPred

0.0026

GERP RS

4.1

Varity_R

0.17

gMVP

0.084

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