18-64017991-C-T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• 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: Benign. The variant received -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 rank	MANE	Protein	UniProt
SERPINB8	NM_001348367.2	c.*3-919C>T		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>T		intron_variant	Intron 7 of 7	5		ENSP00000489949.1

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

African (AFR) AF: 0.509 AC: 21077 AN: 41422

American (AMR) AF: 0.683 AC: 10436 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.616 AC: 2138 AN: 3470

East Asian (EAS) AF: 0.691 AC: 3566 AN: 5160

South Asian (SAS) AF: 0.690 AC: 3325 AN: 4818

European-Finnish (FIN) AF: 0.582 AC: 6132 AN: 10544

Middle Eastern (MID) AF: 0.514 AC: 151 AN: 294

European-Non Finnish (NFE) AF: 0.610 AC: 41438 AN: 67938

Other (OTH) AF: 0.588 AC: 1242 AN: 2114

Alfa AF: 0.598 Hom.: 34445

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
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;