18-63892477-C-T

Position:

• chr18-63892477-C-T

Variant summary

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

The ENST00000299502.9(SERPINB2):​c.168+865C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.264 in 152,110 control chromosomes in the GnomAD database, including 5,774 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 0.26 (5774 hom., cov: 32)
  • Exomes 𝑓: 0.38 (0 hom.)
• Consequence: SERPINB2 ENST00000299502.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.890

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]

LOC124904356 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.463 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SERPINB2	NM_002575.3	c.168+865C>T		intron_variant		ENST00000299502.9	NP_002566.1
LOC124904356	XR_007066466.1	n.183+144G>A		intron_variant, non_coding_transcript_variant
SERPINB2	NM_001143818.2	c.168+865C>T		intron_variant			NP_001137290.1
SERPINB2	XM_024451192.2	c.168+865C>T		intron_variant			XP_024306960.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SERPINB2	ENST00000299502.9	c.168+865C>T		intron_variant		1	NM_002575.3	ENSP00000299502	P1

Frequencies

GnomAD3 genomes AF: 0.264 AC: 40158 AN: 151984 Hom.: 5754 Cov.: 32

Gnomad AFR AF: 0.286

Gnomad AMI AF: 0.124

Gnomad AMR AF: 0.361

Gnomad ASJ AF: 0.184

Gnomad EAS AF: 0.479

Gnomad SAS AF: 0.296

Gnomad FIN AF: 0.234

Gnomad MID AF: 0.361

Gnomad NFE AF: 0.220

Gnomad OTH AF: 0.287

GnomAD4 exome AF: 0.375 AC: 3 AN: 8 Hom.: 0 AF XY: 0.250 AC XY: 1 AN XY: 4

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.500

Gnomad4 NFE exome AF: 0.500

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.264 AC: 40214 AN: 152102 Hom.: 5774 Cov.: 32 AF XY: 0.268 AC XY: 19941 AN XY: 74374

Gnomad4 AFR AF: 0.287

Gnomad4 AMR AF: 0.362

Gnomad4 ASJ AF: 0.184

Gnomad4 EAS AF: 0.479

Gnomad4 SAS AF: 0.297

Gnomad4 FIN AF: 0.234

Gnomad4 NFE AF: 0.220

Gnomad4 OTH AF: 0.293

Alfa AF: 0.234 Hom.: 7201

Bravo AF: 0.277

Asia WGS AF: 0.388 AC: 1346 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.46
DANN	Benign	0.51

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: rs9630856; hg19: chr18-61559711;