18-63891422-C-G

Position:

• chr18-63891422-C-G

Variant summary

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

The NM_002575.3(SERPINB2):​c.-9-14C>G variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.26 in 1,611,838 control chromosomes in the GnomAD database, including 63,354 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 0.37 (12951 hom., cov: 32)
  • Exomes 𝑓: 0.25 (50403 hom.)
• Consequence: SERPINB2 NM_002575.3 splice_polypyrimidine_tract, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.351

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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.638 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SERPINB2	NM_002575.3	c.-9-14C>G		splice_polypyrimidine_tract_variant, intron_variant		ENST00000299502.9	NP_002566.1
LOC124904356	XR_007066466.1	n.183+1199G>C		intron_variant, non_coding_transcript_variant
SERPINB2	NM_001143818.2	c.-9-14C>G		splice_polypyrimidine_tract_variant, intron_variant			NP_001137290.1
SERPINB2	XM_024451192.2	c.-9-14C>G		splice_polypyrimidine_tract_variant, intron_variant			XP_024306960.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SERPINB2	ENST00000299502.9	c.-9-14C>G		splice_polypyrimidine_tract_variant, intron_variant		1	NM_002575.3	ENSP00000299502	P1

Frequencies

GnomAD3 genomes AF: 0.367 AC: 55761 AN: 151842 Hom.: 12910 Cov.: 32

Gnomad AFR AF: 0.644

Gnomad AMI AF: 0.124

Gnomad AMR AF: 0.401

Gnomad ASJ AF: 0.186

Gnomad EAS AF: 0.479

Gnomad SAS AF: 0.297

Gnomad FIN AF: 0.234

Gnomad MID AF: 0.380

Gnomad NFE AF: 0.221

Gnomad OTH AF: 0.365

GnomAD3 exomes AF: 0.307 AC: 76955 AN: 250466 Hom.: 14078 AF XY: 0.293 AC XY: 39656 AN XY: 135406

Gnomad AFR exome AF: 0.654

Gnomad AMR exome AF: 0.443

Gnomad ASJ exome AF: 0.193

Gnomad EAS exome AF: 0.472

Gnomad SAS exome AF: 0.283

Gnomad FIN exome AF: 0.232

Gnomad NFE exome AF: 0.222

Gnomad OTH exome AF: 0.282

GnomAD4 exome AF: 0.248 AC: 362636 AN: 1459878 Hom.: 50403 Cov.: 32 AF XY: 0.248 AC XY: 179820 AN XY: 726274

Gnomad4 AFR exome AF: 0.661

Gnomad4 AMR exome AF: 0.434

Gnomad4 ASJ exome AF: 0.189

Gnomad4 EAS exome AF: 0.406

Gnomad4 SAS exome AF: 0.280

Gnomad4 FIN exome AF: 0.228

Gnomad4 NFE exome AF: 0.221

Gnomad4 OTH exome AF: 0.282

GnomAD4 genome AF: 0.368 AC: 55863 AN: 151960 Hom.: 12951 Cov.: 32 AF XY: 0.368 AC XY: 27353 AN XY: 74296

Gnomad4 AFR AF: 0.644

Gnomad4 AMR AF: 0.401

Gnomad4 ASJ AF: 0.186

Gnomad4 EAS AF: 0.479

Gnomad4 SAS AF: 0.297

Gnomad4 FIN AF: 0.234

Gnomad4 NFE AF: 0.221

Gnomad4 OTH AF: 0.370

Alfa AF: 0.280 Hom.: 1388

Bravo AF: 0.395

Asia WGS AF: 0.417 AC: 1451 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.40
DANN	Benign	0.53

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs6095; hg19: chr18-61558656; COSMIC: COSV55092615; COSMIC: COSV55092615;