rs1509476

Positions:

• chr18-63495126-G-A
• chr18-63495126-G-C
• chr18-63495126-G-T

Variant summary

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

The NM_002639.5(SERPINB5):​c.567+2031G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.739 in 152,150 control chromosomes in the GnomAD database, including 41,986 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 0.74 (41986 hom., cov: 32)
• Consequence: SERPINB5 NM_002639.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.557

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.839 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SERPINB5	NM_002639.5	c.567+2031G>A		intron_variant		ENST00000382771.9
SERPINB5	XM_006722483.4	c.54+2031G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SERPINB5	ENST00000382771.9	c.567+2031G>A		intron_variant		1	NM_002639.5	P1
SERPINB5	ENST00000464346.1	n.249+2031G>A		intron_variant, non_coding_transcript_variant		3
SERPINB5	ENST00000465652.5	n.240+2031G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.739 AC: 112409 AN: 152032 Hom.: 41943 Cov.: 32

Gnomad AFR AF: 0.846

Gnomad AMI AF: 0.746

Gnomad AMR AF: 0.710

Gnomad ASJ AF: 0.683

Gnomad EAS AF: 0.779

Gnomad SAS AF: 0.693

Gnomad FIN AF: 0.655

Gnomad MID AF: 0.722

Gnomad NFE AF: 0.698

Gnomad OTH AF: 0.728

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

GnomAD4 genome AF: 0.739 AC: 112506 AN: 152150 Hom.: 41986 Cov.: 32 AF XY: 0.735 AC XY: 54655 AN XY: 74386

Gnomad4 AFR AF: 0.846

Gnomad4 AMR AF: 0.709

Gnomad4 ASJ AF: 0.683

Gnomad4 EAS AF: 0.779

Gnomad4 SAS AF: 0.692

Gnomad4 FIN AF: 0.655

Gnomad4 NFE AF: 0.698

Gnomad4 OTH AF: 0.731

Alfa AF: 0.718 Hom.: 4871

Bravo AF: 0.745

Asia WGS AF: 0.745 AC: 2592 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.86
DANN	Benign	0.44

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: rs1509476; hg19: chr18-61162359;