18-63979936-C-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_002640.4(SERPINB8):c.304C>T(p.Pro102Ser) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00174 in 1,613,758 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 18/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0011 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0018 ( 2 hom. )

Consequence

SERPINB8
NM_002640.4 missense, splice_region

Scores

Splicing: ADA: 0.0004203

Clinical Significance

Likely benign criteria provided, single submitter B:2

Conservation

PhyloP100: -0.637

Variant links:

Genes affected

SERPINB8 (HGNC:8952): (serpin family B member 8) The protein encoded by this gene is a member of the ov-serpin family of serine protease inhibitors. The encoded protein is produced by platelets and can bind to and inhibit the function of furin, a serine protease involved in platelet functions. In addition, this protein has been found to enhance the mechanical stability of cell-cell adhesion in the skin, and defects in this gene have been associated with an autosomal-recessive form of exfoliative ichthyosis. [provided by RefSeq, Jan 2017]

SERPINB8 links:

HMSD (HGNC:23037): (histocompatibility minor serpin domain containing) This gene encodes a serpin-domain containing protein that may function as a serine protease inhibitor. This gene is primarily expressed in cells of myeloid lineage. A polymorphism in this gene may result in the expression a splice variant that encodes a minor histocompatibility antigen. [provided by RefSeq, Oct 2010]

HMSD links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.007079184).

BP6

Variant 18-63979936-C-T is Benign according to our data. Variant chr18-63979936-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2061790.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SERPINB8	NM_002640.4 link	c.304C>T	p.Pro102Ser	missense_variant, splice_region_variant	Exon 3 of 7	ENST00000397985.7	NP_002631.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SERPINB8	ENST00000397985.7 link	c.304C>T	p.Pro102Ser	missense_variant, splice_region_variant	Exon 3 of 7	1	NM_002640.4	ENSP00000381072.2		P50452-1

Frequencies

GnomAD3 genomes

AF:

0.00108

AC:

165

AN:

152160

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000217

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000189

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00219

Gnomad OTH

AF:

0.000955

GnomAD3 exomes

AF:

0.00128

AC:

322

AN:

250994

Hom.:

AF XY:

0.00113

AC XY:

154

AN XY:

135706

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.000116

Gnomad ASJ exome

AF:

0.000695

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000555

Gnomad NFE exome

AF:

0.00258

Gnomad OTH exome

AF:

0.000654

GnomAD4 exome

AF:

0.00180

AC:

2636

AN:

1461598

Hom.:

Cov.:

AF XY:

0.00178

AC XY:

1293

AN XY:

727120

show subpopulations

Gnomad4 AFR exome

AF:

0.000388

Gnomad4 AMR exome

AF:

0.0000895

Gnomad4 ASJ exome

AF:

0.000765

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000618

Gnomad4 NFE exome

AF:

0.00225

Gnomad4 OTH exome

AF:

0.00101

GnomAD4 genome

AF:

0.00108

AC:

165

AN:

152160

Hom.:

Cov.:

AF XY:

0.00105

AC XY:

AN XY:

74324

show subpopulations

Gnomad4 AFR

AF:

0.000217

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000189

Gnomad4 NFE

AF:

0.00219

Gnomad4 OTH

AF:

0.000955

Alfa

AF:

0.00159

Hom.:

Bravo

AF:

0.000975

TwinsUK

AF:

0.00189

AC:

ALSPAC

AF:

0.00234

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00221

AC:

ExAC

AF:

0.00145

AC:

176

EpiCase

AF:

0.00185

EpiControl

AF:

0.00178

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Dec 15, 2022

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

SERPINB8-related disorder

Benign:1

Apr 13, 2024

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.35

CADD

Benign

8.6

DANN

Benign

0.80

DEOGEN2

Benign

0.12

T;T;.;.;T;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.54

.;T;T;T;T;T

M_CAP

Benign

0.025

MetaRNN

Benign

0.0071

T;T;T;T;T;T

MetaSVM

Benign

-0.88

MutationAssessor

Benign

0.29

N;N;.;N;.;.

PrimateAI

Benign

0.24

PROVEAN

Benign

0.36

N;N;.;N;N;N

REVEL

Benign

0.14

Sift

Benign

0.66

T;T;.;T;T;T

Sift4G

Benign

0.81

T;T;.;T;T;T

Polyphen

0.0030

B;B;.;.;.;.

Vest4

0.11

MVP

0.49

MPC

0.015

ClinPred

0.0090

GERP RS

-0.43

Varity_R

0.050

gMVP

0.17

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00042

dbscSNV1_RF

Benign

0.094

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