rs2289520

Variant names:

• chr18-63493087-G-A
• rs2289520
• NM_002639.5:c.559G>A
• SERPINB5 p.Val187Ile

Your query was ambiguous. Multiple possible variants found:

• chr18-63493087-G-A
• chr18-63493087-G-C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_002639.5(SERPINB5):​c.559G>A​(p.Val187Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SERPINB5 NM_002639.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.330
• Publications: 27 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04249561).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002639.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SERPINB5	NM_002639.5	MANE Select	c.559G>A	p.Val187Ile	missense	Exon 5 of 7	NP_002630.2	P36952-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SERPINB5	ENST00000382771.9	TSL:1 MANE Select	c.559G>A	p.Val187Ile	missense	Exon 5 of 7	ENSP00000372221.4	P36952-1
	SERPINB5	ENST00000489441.5	TSL:1	c.559G>A	p.Val187Ile	missense	Exon 5 of 5	ENSP00000467158.1	P36952-2
	SERPINB5	ENST00000865015.1		c.421G>A	p.Val141Ile	missense	Exon 4 of 6	ENSP00000535074.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 41

GnomAD4 genome Cov.: 32

Alfa AF: 0.00000862 Hom.: 1126

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.072
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	12
DANN	Benign	0.71
DEOGEN2	Benign	0.17	T
Eigen	Benign	-0.70
Eigen_PC	Benign	-0.50
FATHMM_MKL	Benign	0.46	N
LIST_S2	Benign	0.75	T
M_CAP	Benign	0.0027	T
MetaRNN	Benign	0.042	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	-0.63	N
PhyloP100		0.33
PrimateAI	Benign	0.30	T
PROVEAN	Benign	0.77	N
REVEL	Benign	0.043
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Varity_R		0.11
gMVP		0.45
Mutation Taster		=97/3	polymorphism

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2289520;

hg19: chr18-61160320;