chr18-63980245-A-T

Position:

• chr18-63980245-A-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_002640.4(SERPINB8):​c.306+307A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.71 in 152,038 control chromosomes in the GnomAD database, including 39,088 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.71 (39088 hom., cov: 31)
• Consequence: SERPINB8 NM_002640.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.655

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]

HMSD (HGNC:23037): (histocompatibility minor serpin domain containing) This gene encodes a serpin-domain containing protein that may function as a serine protease inhibitor. This gene is primarily expressed in cells of myeloid lineage. A polymorphism in this gene may result in the expression a splice variant that encodes a minor histocompatibility antigen. [provided by RefSeq, Oct 2010]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 18-63980245-A-T is Benign according to our data. Variant chr18-63980245-A-T is described in ClinVar as [Benign]. Clinvar id is 1282685.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.832 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SERPINB8	NM_002640.4	c.306+307A>T		intron_variant		ENST00000397985.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SERPINB8	ENST00000397985.7	c.306+307A>T		intron_variant		1	NM_002640.4	P1

Frequencies

GnomAD3 genomes AF: 0.710 AC: 107804 AN: 151920 Hom.: 39037 Cov.: 31

Gnomad AFR AF: 0.839

Gnomad AMI AF: 0.662

Gnomad AMR AF: 0.600

Gnomad ASJ AF: 0.590

Gnomad EAS AF: 0.496

Gnomad SAS AF: 0.487

Gnomad FIN AF: 0.773

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.686

Gnomad OTH AF: 0.667

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

GnomAD4 genome AF: 0.710 AC: 107910 AN: 152038 Hom.: 39088 Cov.: 31 AF XY: 0.703 AC XY: 52238 AN XY: 74320

Gnomad4 AFR AF: 0.839

Gnomad4 AMR AF: 0.600

Gnomad4 ASJ AF: 0.590

Gnomad4 EAS AF: 0.496

Gnomad4 SAS AF: 0.486

Gnomad4 FIN AF: 0.773

Gnomad4 NFE AF: 0.686

Gnomad4 OTH AF: 0.670

Alfa AF: 0.703 Hom.: 4696

Bravo AF: 0.703

Asia WGS AF: 0.563 AC: 1959 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

Jun 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.7
DANN	Benign	0.53

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: rs1944268; hg19: chr18-61647479;