rs6567355

Variant names:

• chr18-63478364-G-A
• rs6567355
• NM_002639.5:c.-8+1319G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002639.5(SERPINB5):​c.-8+1319G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.701 in 152,056 control chromosomes in the GnomAD database, including 37,905 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 0.70 (37905 hom., cov: 31)
• Consequence: SERPINB5 NM_002639.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.257
• Publications: 3 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: Benign. The variant received -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 = 0.816 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SERPINB5	NM_002639.5	c.-8+1319G>A		intron_variant	Intron 1 of 6	ENST00000382771.9	NP_002630.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SERPINB5	ENST00000382771.9	c.-8+1319G>A		intron_variant	Intron 1 of 6	1	NM_002639.5	ENSP00000372221.4
SERPINB5	ENST00000489441.5	c.-8+1319G>A		intron_variant	Intron 1 of 4	1		ENSP00000467158.1
SERPINB5	ENST00000424602.1	c.-8+1072G>A		intron_variant	Intron 1 of 3	4		ENSP00000408821.1

Frequencies

GnomAD3 genomes AF: 0.701 AC: 106450 AN: 151938 Hom.: 37858 Cov.: 31

Gnomad AFR AF: 0.823

Gnomad AMI AF: 0.713

Gnomad AMR AF: 0.644

Gnomad ASJ AF: 0.626

Gnomad EAS AF: 0.619

Gnomad SAS AF: 0.628

Gnomad FIN AF: 0.622

Gnomad MID AF: 0.690

Gnomad NFE AF: 0.667

Gnomad OTH AF: 0.691

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

GnomAD4 genome AF: 0.701 AC: 106555 AN: 152056 Hom.: 37905 Cov.: 31 AF XY: 0.695 AC XY: 51627 AN XY: 74312

African (AFR) AF: 0.823 AC: 34139 AN: 41490

American (AMR) AF: 0.644 AC: 9838 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.626 AC: 2174 AN: 3472

East Asian (EAS) AF: 0.619 AC: 3191 AN: 5154

South Asian (SAS) AF: 0.628 AC: 3022 AN: 4814

European-Finnish (FIN) AF: 0.622 AC: 6562 AN: 10546

Middle Eastern (MID) AF: 0.714 AC: 210 AN: 294

European-Non Finnish (NFE) AF: 0.666 AC: 45309 AN: 67984

Other (OTH) AF: 0.694 AC: 1461 AN: 2106

Alfa AF: 0.692 Hom.: 4741

Bravo AF: 0.703

Asia WGS AF: 0.660 AC: 2296 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	6.7
DANN	Benign	0.71
PhyloP100		0.26
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6567355; hg19: chr18-61145597;