18-64017991-C-T

Variant summary

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

The NM_001348367.2(SERPINB8):c.*3-919C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.593 in 151,940 control chromosomes in the GnomAD database, including 27,008 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 0.59 (27008 hom., cov: 32)
• Consequence: SERPINB8 NM_001348367.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.627

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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.672 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SERPINB8	NM_001348367.2	c.*3-919C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SERPINB8	ENST00000636430.1	c.*3-919C>T		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.593 AC: 90010 AN: 151822 Hom.: 26982 Cov.: 32

Gnomad AFR AF: 0.509

Gnomad AMI AF: 0.637

Gnomad AMR AF: 0.683

Gnomad ASJ AF: 0.616

Gnomad EAS AF: 0.692

Gnomad SAS AF: 0.690

Gnomad FIN AF: 0.582

Gnomad MID AF: 0.532

Gnomad NFE AF: 0.610

Gnomad OTH AF: 0.583

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

GnomAD4 genome AF: 0.593 AC: 90083 AN: 151940 Hom.: 27008 Cov.: 32 AF XY: 0.595 AC XY: 44211 AN XY: 74262

Gnomad4 AFR AF: 0.509

Gnomad4 AMR AF: 0.683

Gnomad4 ASJ AF: 0.616

Gnomad4 EAS AF: 0.691

Gnomad4 SAS AF: 0.690

Gnomad4 FIN AF: 0.582

Gnomad4 NFE AF: 0.610

Gnomad4 OTH AF: 0.588

Alfa AF: 0.596 Hom.: 29396

Bravo AF: 0.599

Asia WGS AF: 0.681 AC: 2367 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	1.9
Dann	Benign	0.66

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4941236; hg19: chr18-61685225;