Variant 18-63978389-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_002640.4(SERPINB8):c.81C>T(p.Asn27=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0046 in 1,614,156 control chromosomes in the GnomAD database, including 174 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0075 ( 9 hom., cov: 32)

Exomes 𝑓: 0.0043 ( 165 hom. )

Consequence

SERPINB8
NM_002640.4 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.13

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 18-63978389-C-T is Benign according to our data. Variant chr18-63978389-C-T is described in ClinVar as [Benign]. Clinvar id is 778775.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.13 with no splicing effect.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00749 (1140/152284) while in subpopulation SAS AF= 0.0431 (208/4824). AF 95% confidence interval is 0.0383. There are 9 homozygotes in gnomad4. There are 611 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SERPINB8	NM_002640.4 linkuse as main transcript	c.81C>T	p.Asn27=	synonymous_variant	2/7	ENST00000397985.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SERPINB8	ENST00000397985.7 linkuse as main transcript	c.81C>T	p.Asn27=	synonymous_variant	2/7	1	NM_002640.4	P1	P50452-1

Frequencies

GnomAD3 genomes

AF:

0.00748

AC:

1138

AN:

152166

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0186

Gnomad AMI

AF:

0.00769

Gnomad AMR

AF:

0.00334

Gnomad ASJ

AF:

0.0124

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.0437

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000544

Gnomad OTH

AF:

0.00716

GnomAD3 exomes

AF:

0.00832

AC:

2092

AN:

251448

Hom.:

AF XY:

0.0100

AC XY:

1360

AN XY:

135900

show subpopulations

Gnomad AFR exome

AF:

0.0193

Gnomad AMR exome

AF:

0.00179

Gnomad ASJ exome

AF:

0.0124

Gnomad EAS exome

AF:

0.000381

Gnomad SAS exome

AF:

0.0475

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000879

Gnomad OTH exome

AF:

0.00489

GnomAD4 exome

AF:

0.00429

AC:

6278

AN:

1461872

Hom.:

165

Cov.:

AF XY:

0.00553

AC XY:

4024

AN XY:

727244

show subpopulations

Gnomad4 AFR exome

AF:

0.0214

Gnomad4 AMR exome

AF:

0.00195

Gnomad4 ASJ exome

AF:

0.0140

Gnomad4 EAS exome

AF:

0.000176

Gnomad4 SAS exome

AF:

0.0473

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.000501

Gnomad4 OTH exome

AF:

0.00682

GnomAD4 genome

AF:

0.00749

AC:

1140

AN:

152284

Hom.:

Cov.:

AF XY:

0.00821

AC XY:

611

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.0187

Gnomad4 AMR

AF:

0.00333

Gnomad4 ASJ

AF:

0.0124

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.0431

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000544

Gnomad4 OTH

AF:

0.00662

Alfa

AF:

0.00461

Hom.:

Bravo

AF:

0.00761

Asia WGS

AF:

0.0240

AC:

AN:

3478

EpiCase

AF:

0.00158

EpiControl

AF:

0.000889

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Oct 07, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.16

DANN

Benign

0.48

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