18-64017991-C-G

Variant names:

• chr18-64017991-C-G
• rs4941236
• NM_001348367.2:c.*3-919C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001348367.2(SERPINB8):​c.*3-919C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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)
• Consequence: SERPINB8 NM_001348367.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.627
• Publications: 2 publications found

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: AR, Unknown, AD Classification: STRONG, MODERATE, LIMITED Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), Ambry Genetics, Genomics England PanelApp, G2P
• exfoliative ichthyosis

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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=-0.88).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SERPINB8	NM_001348367.2	c.*3-919C>G		intron_variant	Intron 7 of 7		NP_001335296.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SERPINB8	ENST00000636430.1	c.*3-919C>G		intron_variant	Intron 7 of 7	5		ENSP00000489949.1

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.7
DANN	Benign	0.60
PhyloP100		-0.63

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs4941236; hg19: chr18-61685225;