rs1509478

Positions:

• chr18-63496899-C-G

Variant summary

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

The NM_002639.5(SERPINB5):​c.568-2221C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.543 in 323,010 control chromosomes in the GnomAD database, including 49,630 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 0.53 (22582 hom., cov: 32)
  • Exomes 𝑓: 0.55 (27048 hom.)
• Consequence: SERPINB5 NM_002639.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.27

Genes affected

SERPINB5 (HGNC:8949): (serpin family B member 5) Predicted to enable serine-type endopeptidase inhibitor activity. Predicted to be involved in negative regulation of endopeptidase activity. Predicted to act upstream of or within several processes, including extracellular matrix organization; prostate gland morphogenesis; and regulation of epithelial cell proliferation. Located in cytoplasm. Biomarker of hepatocellular carcinoma. [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=-0.96).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.62 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SERPINB5	NM_002639.5	c.568-2221C>G		intron_variant		ENST00000382771.9
SERPINB5	XM_006722483.4	c.55-2221C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SERPINB5	ENST00000382771.9	c.568-2221C>G		intron_variant		1	NM_002639.5	P1
SERPINB5	ENST00000464346.1	n.250-2221C>G		intron_variant, non_coding_transcript_variant		3
SERPINB5	ENST00000465652.5	n.241-2221C>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.534 AC: 81187 AN: 151902 Hom.: 22576 Cov.: 32

Gnomad AFR AF: 0.380

Gnomad AMI AF: 0.542

Gnomad AMR AF: 0.532

Gnomad ASJ AF: 0.585

Gnomad EAS AF: 0.527

Gnomad SAS AF: 0.392

Gnomad FIN AF: 0.613

Gnomad MID AF: 0.472

Gnomad NFE AF: 0.625

Gnomad OTH AF: 0.537

GnomAD4 exome AF: 0.552 AC: 94315 AN: 170990 Hom.: 27048 AF XY: 0.532 AC XY: 51111 AN XY: 96034

Gnomad4 AFR exome AF: 0.373

Gnomad4 AMR exome AF: 0.510

Gnomad4 ASJ exome AF: 0.574

Gnomad4 EAS exome AF: 0.529

Gnomad4 SAS exome AF: 0.384

Gnomad4 FIN exome AF: 0.618

Gnomad4 NFE exome AF: 0.617

Gnomad4 OTH exome AF: 0.569

GnomAD4 genome AF: 0.534 AC: 81217 AN: 152020 Hom.: 22582 Cov.: 32 AF XY: 0.531 AC XY: 39434 AN XY: 74324

Gnomad4 AFR AF: 0.380

Gnomad4 AMR AF: 0.531

Gnomad4 ASJ AF: 0.585

Gnomad4 EAS AF: 0.527

Gnomad4 SAS AF: 0.392

Gnomad4 FIN AF: 0.613

Gnomad4 NFE AF: 0.625

Gnomad4 OTH AF: 0.542

Alfa AF: 0.573 Hom.: 3131

Bravo AF: 0.524

Asia WGS AF: 0.477 AC: 1656 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	5.5
DANN	Benign	0.42

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: rs1509478; hg19: chr18-61164132;