Genetic Variant SERPINB8:c.306+94C>G (chr18-63980032-C-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_002640.4(SERPINB8):c.306+94C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000009 in 1,111,592 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)

Exomes 𝑓: 9.0e-7 ( 0 hom. )

Consequence

SERPINB8
NM_002640.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0730

Publications

0 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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002640.4. 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_002640.4	MANE Select	c.306+94C>G	intron	N/A	NP_002631.3
SERPINB8	NM_001366198.1		c.306+94C>G	intron	N/A	NP_001353127.1	P50452-1
SERPINB8	NM_198833.2		c.306+94C>G	intron	N/A	NP_942130.1	P50452-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SERPINB8	ENST00000397985.7	TSL:1 MANE Select	c.306+94C>G	intron	N/A	ENSP00000381072.2	P50452-1
SERPINB8	ENST00000397988.7	TSL:1	c.306+94C>G	intron	N/A	ENSP00000381075.3	P50452-2
SERPINB8	ENST00000353706.6	TSL:5	c.306+94C>G	intron	N/A	ENSP00000331368.3	P50452-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

9.00e-7

AC:

AN:

1111592

Hom.:

AF XY:

0.00

AC XY:

AN XY:

559164

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

25118

American (AMR)

AF:

0.00

AC:

AN:

33496

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20852

East Asian (EAS)

AF:

0.00

AC:

AN:

37082

South Asian (SAS)

AF:

0.00

AC:

AN:

69960

European-Finnish (FIN)

AF:

0.00

AC:

AN:

45298

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3938

European-Non Finnish (NFE)

AF:

0.00000121

AC:

AN:

828002

Other (OTH)

AF:

0.00

AC:

AN:

47846

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.225

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

1.3

(source)

DANN

Benign

0.33

PhyloP100

-0.073

PromoterAI

-0.0038

Neutral

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over