rs1944270

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_002640.4(SERPINB8):c.203G>A(p.Arg68Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.293 in 1,613,444 control chromosomes in the GnomAD database, including 73,670 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.36 ( 11361 hom., cov: 32)

Exomes 𝑓: 0.29 ( 62309 hom. )

Consequence

SERPINB8
NM_002640.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -2.36

Publications

38 publications found

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 was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.19396855E-5).

BP6

Variant 18-63979835-G-A is Benign according to our data. Variant chr18-63979835-G-A is described in ClinVar as Benign. ClinVar VariationId is 1262057.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.569 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SERPINB8	NM_002640.4 link	c.203G>A	p.Arg68Gln	missense_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.203G>A	p.Arg68Gln	missense_variant	Exon 3 of 7	1	NM_002640.4	ENSP00000381072.2		P50452-1

Frequencies

GnomAD3 genomes

AF:

0.360

AC:

54692

AN:

151890

Hom.:

11335

Cov.:

show subpopulations

Gnomad AFR

AF:

0.575

Gnomad AMI

AF:

0.315

Gnomad AMR

AF:

0.270

Gnomad ASJ

AF:

0.307

Gnomad EAS

AF:

0.190

Gnomad SAS

AF:

0.182

Gnomad FIN

AF:

0.338

Gnomad MID

AF:

0.231

Gnomad NFE

AF:

0.284

Gnomad OTH

AF:

0.299

GnomAD2 exomes

AF:

0.291

AC:

73105

AN:

251286

AF XY:

0.283

show subpopulations

Gnomad AFR exome

AF:

0.582

Gnomad AMR exome

AF:

0.270

Gnomad ASJ exome

AF:

0.307

Gnomad EAS exome

AF:

0.183

Gnomad FIN exome

AF:

0.344

Gnomad NFE exome

AF:

0.289

Gnomad OTH exome

AF:

0.275

GnomAD4 exome

AF:

0.286

AC:

417264

AN:

1461436

Hom.:

62309

Cov.:

AF XY:

0.282

AC XY:

204717

AN XY:

727066

show subpopulations

African (AFR)

AF:

0.586

AC:

19606

AN:

33466

American (AMR)

AF:

0.267

AC:

11936

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.310

AC:

8108

AN:

26130

East Asian (EAS)

AF:

0.214

AC:

8487

AN:

39692

South Asian (SAS)

AF:

0.196

AC:

16920

AN:

86246

European-Finnish (FIN)

AF:

0.349

AC:

18652

AN:

53384

Middle Eastern (MID)

AF:

0.244

AC:

1407

AN:

5768

European-Non Finnish (NFE)

AF:

0.283

AC:

314911

AN:

1111654

Other (OTH)

AF:

0.285

AC:

17237

AN:

60376

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

14632

29264

43897

58529

73161

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10452

20904

31356

41808

52260

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.360

AC:

54766

AN:

152008

Hom.:

11361

Cov.:

AF XY:

0.355

AC XY:

26361

AN XY:

74306

show subpopulations

African (AFR)

AF:

0.575

AC:

23832

AN:

41412

American (AMR)

AF:

0.270

AC:

4128

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.307

AC:

1067

AN:

3472

East Asian (EAS)

AF:

0.189

AC:

978

AN:

5164

South Asian (SAS)

AF:

0.181

AC:

872

AN:

4816

European-Finnish (FIN)

AF:

0.338

AC:

3576

AN:

10570

Middle Eastern (MID)

AF:

0.235

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.284

AC:

19319

AN:

67958

Other (OTH)

AF:

0.302

AC:

638

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1667

3334

5000

6667

8334

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

502

1004

1506

2008

2510

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.318

Hom.:

18817

Bravo

AF:

0.367

TwinsUK

AF:

0.280

AC:

1040

ALSPAC

AF:

0.283

AC:

1089

ESP6500AA

AF:

0.573

AC:

2526

ESP6500EA

AF:

0.280

AC:

2409

ExAC

AF:

0.301

AC:

36517

Asia WGS

AF:

0.232

AC:

811

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Feb 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

May 04, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Peeling skin syndrome 5

Benign:1

Jul 15, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.075

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.42

CADD

Benign

4.3

(source)

DANN

Benign

0.79

DEOGEN2

Benign

0.082

T;T;.;.;T;T

Eigen

Benign

-2.0

Eigen_PC

Benign

-2.0

FATHMM_MKL

Benign

0.041

LIST_S2

Benign

0.083

.;T;T;T;T;T

MetaRNN

Benign

0.000012

T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.98

N;N;.;N;.;.

PhyloP100

-2.4

PrimateAI

Benign

0.18

PROVEAN

Benign

2.2

N;N;.;N;N;N

REVEL

Uncertain

0.30

Sift

Benign

1.0

T;T;.;T;T;T

Sift4G

Benign

0.91

T;T;.;T;T;T

Polyphen

0.0

B;B;.;.;.;.

Vest4

0.013

MPC

0.015

ClinPred

0.00088

GERP RS

-5.6

PromoterAI

-0.049

Neutral

(source)

Varity_R

0.030

gMVP

0.059

Mutation Taster

=299/1

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over