18-63901736-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_002575.3(SERPINB2):c.536-4G>A variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00411 in 1,536,562 control chromosomes in the GnomAD database, including 251 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.022 (145 hom., cov: 32)
  • Exomes 𝑓: 0.0021 (106 hom.)
• Consequence: SERPINB2 NM_002575.3 splice_region, splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.0001054
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.70

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 18-63901736-G-A is Benign according to our data. Variant chr18-63901736-G-A is described in ClinVar as [Benign]. Clinvar id is 780481.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0755 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SERPINB2	NM_002575.3	c.536-4G>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000299502.9
SERPINB2	NM_001143818.2	c.536-4G>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant
SERPINB2	XM_024451192.2	c.536-4G>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SERPINB2	ENST00000299502.9	c.536-4G>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_002575.3	P1
SERPINB2	ENST00000457692.5	c.536-4G>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		5		P1
SERPINB2	ENST00000482254.1	n.492-4G>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0225 AC: 3415 AN: 152084 Hom.: 145 Cov.: 32

Gnomad AFR AF: 0.0779

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00905

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000206

Gnomad OTH AF: 0.0187

GnomAD3 exomes AF: 0.00597 AC: 1131 AN: 189408 Hom.: 55 AF XY: 0.00391 AC XY: 409 AN XY: 104594

Gnomad AFR exome AF: 0.0795

Gnomad AMR exome AF: 0.00397

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000480

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000146

Gnomad OTH exome AF: 0.00358

GnomAD4 exome AF: 0.00209 AC: 2891 AN: 1384360 Hom.: 106 Cov.: 29 AF XY: 0.00185 AC XY: 1269 AN XY: 685976

Gnomad4 AFR exome AF: 0.0845

Gnomad4 AMR exome AF: 0.00451

Gnomad4 ASJ exome AF: 0.0000428

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000840

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000572

Gnomad4 OTH exome AF: 0.00505

GnomAD4 genome AF: 0.0225 AC: 3418 AN: 152202 Hom.: 145 Cov.: 32 AF XY: 0.0218 AC XY: 1624 AN XY: 74412

Gnomad4 AFR AF: 0.0777

Gnomad4 AMR AF: 0.00904

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000206

Gnomad4 OTH AF: 0.0185

Alfa AF: 0.00604 Hom.: 39

Bravo AF: 0.0256

Asia WGS AF: 0.00231 AC: 8 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	0.44
Dann	Benign	0.58

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00011
dbscSNV1_RF	Benign	0.0
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: rs6099; hg19: chr18-61568970;