Variant 18-63902944-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_002575.3(SERPINB2):c.887G>A(p.Ser296Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000533 in 1,612,864 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000099 ( 1 hom., cov: 32)

Exomes 𝑓: 0.000049 ( 2 hom. )

Consequence

SERPINB2
NM_002575.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.36

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 -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.030152947).

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
SERPINB2	NM_002575.3 linkuse as main transcript	c.887G>A	p.Ser296Asn	missense_variant	8/8	ENST00000299502.9	NP_002566.1
SERPINB2	NM_001143818.2 linkuse as main transcript	c.887G>A	p.Ser296Asn	missense_variant	9/9		NP_001137290.1
SERPINB2	XM_024451192.2 linkuse as main transcript	c.887G>A	p.Ser296Asn	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.887G>A	p.Ser296Asn	missense_variant	8/8	1	NM_002575.3	ENSP00000299502	P1
SERPINB2	ENST00000457692.5 linkuse as main transcript	c.887G>A	p.Ser296Asn	missense_variant	9/9	5		ENSP00000401645	P1

Frequencies

GnomAD3 genomes

AF:

0.0000986

AC:

AN:

152156

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000721

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.0000602

AC:

AN:

249312

Hom.:

AF XY:

0.0000520

AC XY:

AN XY:

134664

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000117

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000164

Gnomad SAS exome

AF:

0.000164

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000267

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000486

AC:

AN:

1460708

Hom.:

Cov.:

AF XY:

0.0000578

AC XY:

AN XY:

726614

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000897

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000151

Gnomad4 SAS exome

AF:

0.000128

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000135

Gnomad4 OTH exome

AF:

0.000564

GnomAD4 genome

AF:

0.0000986

AC:

AN:

152156

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74318

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000721

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.0000282

Hom.:

Bravo

AF:

0.0000416

ExAC

AF:

0.0000741

AC:

Asia WGS

AF:

0.00577

AC:

AN:

3478

EpiCase

AF:

0.0000546

EpiControl

AF:

0.000119

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 06, 2023

The c.887G>A (p.S296N) alteration is located in exon 9 (coding exon 7) of the SERPINB2 gene. This alteration results from a G to A substitution at nucleotide position 887, causing the serine (S) at amino acid position 296 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.090

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.66

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.11

T;T

Eigen

Benign

-0.61

Eigen_PC

Benign

-0.54

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.51

.;T

M_CAP

Benign

0.0032

MetaRNN

Benign

0.030

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.5

L;L

MutationTaster

Benign

0.99

N;N

PrimateAI

Benign

0.40

PROVEAN

Benign

-0.14

N;N

REVEL

Benign

0.017

Sift

Benign

0.26

T;T

Sift4G

Benign

0.68

T;T

Polyphen

0.0050

B;B

Vest4

0.069

MutPred

0.39

Loss of ubiquitination at K297 (P = 0.0505);Loss of ubiquitination at K297 (P = 0.0505);

MVP

0.081

MPC

0.020

ClinPred

0.017

GERP RS

1.6

Varity_R

0.19

gMVP

0.24

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over