18-63883351-G-T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000404622.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SERPINB2	ENST00000404622.5	TSL:5	c.-267-6487G>T		intron	N/A	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

African (AFR) AF: 0.364 AC: 15094 AN: 41426

American (AMR) AF: 0.372 AC: 5671 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.184 AC: 637 AN: 3466

East Asian (EAS) AF: 0.478 AC: 2468 AN: 5166

South Asian (SAS) AF: 0.297 AC: 1424 AN: 4802

European-Finnish (FIN) AF: 0.235 AC: 2481 AN: 10550

Middle Eastern (MID) AF: 0.363 AC: 106 AN: 292

European-Non Finnish (NFE) AF: 0.220 AC: 14940 AN: 67960

Other (OTH) AF: 0.311 AC: 659 AN: 2116

Alfa AF: 0.227 Hom.: 1591

Bravo AF: 0.303

Asia WGS AF: 0.390 AC: 1354 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.5
DANN	Benign	0.28
PhyloP100		0.037

Splicing

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

Other links and lift over

dbSNP: rs9946657; hg19: chr18-61550585;