18-63981936-A-G

Position:

• chr18-63981936-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_002640.4(SERPINB8):​c.424+98A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.165 in 764,884 control chromosomes in the GnomAD database, including 12,433 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.20 (3845 hom., cov: 32)
  • Exomes 𝑓: 0.16 (8588 hom.)
• Consequence: SERPINB8 NM_002640.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.691

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 18-63981936-A-G is Benign according to our data. Variant chr18-63981936-A-G is described in ClinVar as [Benign]. Clinvar id is 1250123.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.339 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SERPINB8	NM_002640.4	c.424+98A>G		intron_variant		ENST00000397985.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SERPINB8	ENST00000397985.7	c.424+98A>G		intron_variant		1	NM_002640.4	P1

Frequencies

GnomAD3 genomes AF: 0.203 AC: 30828 AN: 152008 Hom.: 3829 Cov.: 32

Gnomad AFR AF: 0.344

Gnomad AMI AF: 0.0954

Gnomad AMR AF: 0.101

Gnomad ASJ AF: 0.143

Gnomad EAS AF: 0.0854

Gnomad SAS AF: 0.107

Gnomad FIN AF: 0.258

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.153

Gnomad OTH AF: 0.165

GnomAD4 exome AF: 0.155 AC: 95115 AN: 612758 Hom.: 8588 AF XY: 0.151 AC XY: 49304 AN XY: 325948

Gnomad4 AFR exome AF: 0.341

Gnomad4 AMR exome AF: 0.0970

Gnomad4 ASJ exome AF: 0.151

Gnomad4 EAS exome AF: 0.0811

Gnomad4 SAS exome AF: 0.110

Gnomad4 FIN exome AF: 0.258

Gnomad4 NFE exome AF: 0.156

Gnomad4 OTH exome AF: 0.157

GnomAD4 genome AF: 0.203 AC: 30896 AN: 152126 Hom.: 3845 Cov.: 32 AF XY: 0.200 AC XY: 14890 AN XY: 74356

Gnomad4 AFR AF: 0.344

Gnomad4 AMR AF: 0.101

Gnomad4 ASJ AF: 0.143

Gnomad4 EAS AF: 0.0858

Gnomad4 SAS AF: 0.107

Gnomad4 FIN AF: 0.258

Gnomad4 NFE AF: 0.153

Gnomad4 OTH AF: 0.168

Alfa AF: 0.160 Hom.: 1871

Bravo AF: 0.201

Asia WGS AF: 0.138 AC: 482 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 15, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.0020
DANN	Benign	0.43

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

LitVar

Other links and lift over

dbSNP: rs12605976; hg19: chr18-61649170;