Genetic Variant SERPINB8:c.720+4306T>C (chr18-63989551-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001348367.2(SERPINB8):c.720+4306T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.417 in 151,930 control chromosomes in the GnomAD database, including 14,766 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.42 ( 14766 hom., cov: 31)

Consequence

SERPINB8
NM_001348367.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.01

Publications

13 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 Gene-Disease associations (from GenCC):

peeling skin syndrome 5
Inheritance: Unknown, AR, AD Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia, Genomics England PanelApp, G2P, Ambry Genetics
exfoliative ichthyosis
Inheritance: AR Classification: SUPPORTIVE, LIMITED Submitted by: Orphanet, ClinGen

SERPINB8 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.99).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.638 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001348367.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SERPINB8	NM_001348367.2		c.720+4306T>C	intron	N/A	NP_001335296.1	A0A1B0GU38
SERPINB8	NM_002640.4	MANE Select	c.*2273T>C	downstream_gene	N/A	NP_002631.3
SERPINB8	NM_001366198.1		c.*2273T>C	downstream_gene	N/A	NP_001353127.1	P50452-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SERPINB8	ENST00000636430.1	TSL:5	c.720+4306T>C	intron	N/A	ENSP00000489949.1	A0A1B0GU38
SERPINB8	ENST00000493661.2	TSL:3	c.69+4306T>C	intron	N/A	ENSP00000478199.1	A0A087WTX6
SERPINB8	ENST00000397985.7	TSL:1 MANE Select	c.*2273T>C	downstream_gene	N/A	ENSP00000381072.2	P50452-1

Frequencies

GnomAD3 genomes

AF:

0.417

AC:

63266

AN:

151812

Hom.:

14730

Cov.:

show subpopulations

Gnomad AFR

AF:

0.644

Gnomad AMI

AF:

0.237

Gnomad AMR

AF:

0.405

Gnomad ASJ

AF:

0.290

Gnomad EAS

AF:

0.286

Gnomad SAS

AF:

0.302

Gnomad FIN

AF:

0.337

Gnomad MID

AF:

0.418

Gnomad NFE

AF:

0.321

Gnomad OTH

AF:

0.414

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.417

AC:

63362

AN:

151930

Hom.:

14766

Cov.:

AF XY:

0.414

AC XY:

30750

AN XY:

74236

show subpopulations

African (AFR)

AF:

0.645

AC:

26679

AN:

41388

American (AMR)

AF:

0.404

AC:

6181

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.290

AC:

1006

AN:

3470

East Asian (EAS)

AF:

0.286

AC:

1473

AN:

5154

South Asian (SAS)

AF:

0.302

AC:

1455

AN:

4820

European-Finnish (FIN)

AF:

0.337

AC:

3551

AN:

10540

Middle Eastern (MID)

AF:

0.429

AC:

126

AN:

294

European-Non Finnish (NFE)

AF:

0.321

AC:

21792

AN:

67956

Other (OTH)

AF:

0.418

AC:

883

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1740

3480

5221

6961

8701

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

570

1140

1710

2280

2850

<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:

0.354

Hom.:

21405

Bravo

AF:

0.434

Asia WGS

AF:

0.377

AC:

1314

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.99

CADD

Benign

0.83

(source)

DANN

Benign

0.35

PhyloP100

-1.0

Splicing

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over