18-63989551-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.01

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SERPINB8	NM_001348367.2	c.720+4306T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SERPINB8	ENST00000493661.2	c.70+4306T>C		intron_variant		3
SERPINB8	ENST00000636430.1	c.720+4306T>C		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.417 AC: 63266 AN: 151812 Hom.: 14730 Cov.: 31

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.: 31 AF XY: 0.414 AC XY: 30750 AN XY: 74236

Gnomad4 AFR AF: 0.645

Gnomad4 AMR AF: 0.404

Gnomad4 ASJ AF: 0.290

Gnomad4 EAS AF: 0.286

Gnomad4 SAS AF: 0.302

Gnomad4 FIN AF: 0.337

Gnomad4 NFE AF: 0.321

Gnomad4 OTH AF: 0.418

Alfa AF: 0.337 Hom.: 4999

Bravo AF: 0.434

Asia WGS AF: 0.377 AC: 1314 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
Cadd	Benign	0.83
Dann	Benign	0.35

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs514315; hg19: chr18-61656785;