18-63883351-G-T

Variant names:

• chr18-63883351-G-T
• rs9946657
• ENST00000404622.5:c.-267-6487G>T

Variant summary

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

The ENST00000404622.5(SERPINB2):​c.-267-6487G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.287 in 151,954 control chromosomes in the GnomAD database, including 6,857 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 0.29 (6857 hom., cov: 32)
• Consequence: SERPINB2 ENST00000404622.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0370

Genes affected

SERPINB2 (HGNC:8584): (serpin family B member 2) Predicted to enable serine-type endopeptidase inhibitor activity. Predicted to be involved in negative regulation of endopeptidase activity. Predicted to be located in extracellular region and plasma membrane. Predicted to be active in extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.462 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SERPINB2	ENST00000404622.5	c.-267-6487G>T		intron_variant	Intron 1 of 4	5		ENSP00000385397.1

Frequencies

GnomAD3 genomes AF: 0.287 AC: 43536 AN: 151838 Hom.: 6836 Cov.: 32

Gnomad AFR AF: 0.364

Gnomad AMI AF: 0.124

Gnomad AMR AF: 0.371

Gnomad ASJ AF: 0.184

Gnomad EAS AF: 0.478

Gnomad SAS AF: 0.296

Gnomad FIN AF: 0.235

Gnomad MID AF: 0.361

Gnomad NFE AF: 0.220

Gnomad OTH AF: 0.306

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

GnomAD4 genome AF: 0.287 AC: 43593 AN: 151954 Hom.: 6857 Cov.: 32 AF XY: 0.290 AC XY: 21543 AN XY: 74274

Gnomad4 AFR AF: 0.364

Gnomad4 AMR AF: 0.372

Gnomad4 ASJ AF: 0.184

Gnomad4 EAS AF: 0.478

Gnomad4 SAS AF: 0.297

Gnomad4 FIN AF: 0.235

Gnomad4 NFE AF: 0.220

Gnomad4 OTH AF: 0.311

Alfa AF: 0.213 Hom.: 1279

Bravo AF: 0.303

Asia WGS AF: 0.390 AC: 1354 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.5
DANN	Benign	0.28

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs9946657; hg19: chr18-61550585;