Variant chr18-63983631-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_002640.4(SERPINB8):c.477G>A(p.Leu159=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.299 in 1,612,234 control chromosomes in the GnomAD database, including 75,361 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.25 ( 5390 hom., cov: 32)

Exomes 𝑓: 0.30 ( 69971 hom. )

Consequence

SERPINB8
NM_002640.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.316

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.54).

BP6

Variant 18-63983631-G-A is Benign according to our data. Variant chr18-63983631-G-A is described in ClinVar as [Benign]. Clinvar id is 1263303.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.316 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.311 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SERPINB8	NM_002640.4 linkuse as main transcript	c.477G>A	p.Leu159=	synonymous_variant	5/7	ENST00000397985.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SERPINB8	ENST00000397985.7 linkuse as main transcript	c.477G>A	p.Leu159=	synonymous_variant	5/7	1	NM_002640.4	P1	P50452-1

Frequencies

GnomAD3 genomes

AF:

0.247

AC:

37548

AN:

151944

Hom.:

5387

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0916

Gnomad AMI

AF:

0.340

Gnomad AMR

AF:

0.272

Gnomad ASJ

AF:

0.224

Gnomad EAS

AF:

0.300

Gnomad SAS

AF:

0.222

Gnomad FIN

AF:

0.365

Gnomad MID

AF:

0.258

Gnomad NFE

AF:

0.314

Gnomad OTH

AF:

0.278

GnomAD3 exomes

AF:

0.279

AC:

70148

AN:

251404

Hom.:

10448

AF XY:

0.280

AC XY:

38009

AN XY:

135872

show subpopulations

Gnomad AFR exome

AF:

0.0903

Gnomad AMR exome

AF:

0.255

Gnomad ASJ exome

AF:

0.210

Gnomad EAS exome

AF:

0.298

Gnomad SAS exome

AF:

0.216

Gnomad FIN exome

AF:

0.363

Gnomad NFE exome

AF:

0.317

Gnomad OTH exome

AF:

0.282

GnomAD4 exome

AF:

0.304

AC:

444121

AN:

1460168

Hom.:

69971

Cov.:

AF XY:

0.301

AC XY:

218692

AN XY:

726502

show subpopulations

Gnomad4 AFR exome

AF:

0.0855

Gnomad4 AMR exome

AF:

0.256

Gnomad4 ASJ exome

AF:

0.208

Gnomad4 EAS exome

AF:

0.249

Gnomad4 SAS exome

AF:

0.216

Gnomad4 FIN exome

AF:

0.361

Gnomad4 NFE exome

AF:

0.321

Gnomad4 OTH exome

AF:

0.303

GnomAD4 genome

AF:

0.247

AC:

37562

AN:

152066

Hom.:

5390

Cov.:

AF XY:

0.250

AC XY:

18564

AN XY:

74334

show subpopulations

Gnomad4 AFR

AF:

0.0914

Gnomad4 AMR

AF:

0.273

Gnomad4 ASJ

AF:

0.224

Gnomad4 EAS

AF:

0.301

Gnomad4 SAS

AF:

0.223

Gnomad4 FIN

AF:

0.365

Gnomad4 NFE

AF:

0.314

Gnomad4 OTH

AF:

0.281

Alfa

AF:

0.262

Hom.:

3060

Bravo

AF:

0.233

Asia WGS

AF:

0.273

AC:

946

AN:

3478

EpiCase

AF:

0.300

EpiControl

AF:

0.306

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 29, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 04, 2021	- -

Peeling skin syndrome 5

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 15, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.54

CADD

Benign

8.2

DANN

Benign

0.67

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