18-63980245-A-T

Variant names:

• chr18-63980245-A-T
• rs1944268
• NM_002640.4:c.306+307A>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 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]

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

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002640.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SERPINB8	NM_002640.4	MANE Select	c.306+307A>T		intron	N/A	NP_002631.3
	SERPINB8	NM_001366198.1		c.306+307A>T		intron	N/A	NP_001353127.1	P50452-1
	SERPINB8	NM_198833.2		c.306+307A>T		intron	N/A	NP_942130.1	P50452-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SERPINB8	ENST00000397985.7	TSL:1 MANE Select	c.306+307A>T		intron	N/A	ENSP00000381072.2	P50452-1
	SERPINB8	ENST00000397988.7	TSL:1	c.306+307A>T		intron	N/A	ENSP00000381075.3	P50452-2
	SERPINB8	ENST00000353706.6	TSL:5	c.306+307A>T		intron	N/A	ENSP00000331368.3	P50452-1

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

African (AFR) AF: 0.839 AC: 34802 AN: 41486

American (AMR) AF: 0.600 AC: 9178 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.590 AC: 2047 AN: 3468

East Asian (EAS) AF: 0.496 AC: 2560 AN: 5158

South Asian (SAS) AF: 0.486 AC: 2337 AN: 4808

European-Finnish (FIN) AF: 0.773 AC: 8162 AN: 10560

Middle Eastern (MID) AF: 0.571 AC: 168 AN: 294

European-Non Finnish (NFE) AF: 0.686 AC: 46647 AN: 67968

Other (OTH) AF: 0.670 AC: 1407 AN: 2100

Alfa AF: 0.703 Hom.: 4696

Bravo AF: 0.703

Asia WGS AF: 0.563 AC: 1959 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.7
DANN	Benign	0.53
PhyloP100		-0.66
PromoterAI		-0.016	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1944268; hg19: chr18-61647479;