rs1015416

Positions:

• chr18-63902149-A-C
• chr18-63902149-A-T

Variant summary

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

The NM_002575.3(SERPINB2):​c.679-255A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.373 in 152,062 control chromosomes in the GnomAD database, including 13,485 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 (13485 hom., cov: 32)
• Consequence: SERPINB2 NM_002575.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.372

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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.655 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SERPINB2	NM_002575.3	c.679-255A>C		intron_variant		ENST00000299502.9
SERPINB2	NM_001143818.2	c.679-255A>C		intron_variant
SERPINB2	XM_024451192.2	c.679-255A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SERPINB2	ENST00000299502.9	c.679-255A>C		intron_variant		1	NM_002575.3	P1
SERPINB2	ENST00000457692.5	c.679-255A>C		intron_variant		5		P1
SERPINB2	ENST00000482254.1	n.635-255A>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.373 AC: 56619 AN: 151944 Hom.: 13441 Cov.: 32

Gnomad AFR AF: 0.662

Gnomad AMI AF: 0.124

Gnomad AMR AF: 0.404

Gnomad ASJ AF: 0.189

Gnomad EAS AF: 0.479

Gnomad SAS AF: 0.297

Gnomad FIN AF: 0.233

Gnomad MID AF: 0.383

Gnomad NFE AF: 0.222

Gnomad OTH AF: 0.370

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

GnomAD4 genome AF: 0.373 AC: 56723 AN: 152062 Hom.: 13485 Cov.: 32 AF XY: 0.374 AC XY: 27770 AN XY: 74350

Gnomad4 AFR AF: 0.662

Gnomad4 AMR AF: 0.404

Gnomad4 ASJ AF: 0.189

Gnomad4 EAS AF: 0.479

Gnomad4 SAS AF: 0.298

Gnomad4 FIN AF: 0.233

Gnomad4 NFE AF: 0.222

Gnomad4 OTH AF: 0.375

Alfa AF: 0.229 Hom.: 1040

Bravo AF: 0.401

Asia WGS AF: 0.427 AC: 1485 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.37
DANN	Benign	0.48

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: rs1015416; hg19: chr18-61569383;