18-63478474-C-T

Position:

• chr18-63478474-C-T

Variant summary

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

The NM_002639.5(SERPINB5):​c.-8+1429C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00961 in 152,306 control chromosomes in the GnomAD database, including 72 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 0.0096 (72 hom., cov: 32)
• Consequence: SERPINB5 NM_002639.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.622

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0741 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SERPINB5	NM_002639.5	c.-8+1429C>T		intron_variant		ENST00000382771.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SERPINB5	ENST00000382771.9	c.-8+1429C>T		intron_variant		1	NM_002639.5	P1
SERPINB5	ENST00000489441.5	c.-8+1429C>T		intron_variant		1
SERPINB5	ENST00000424602.1	c.-8+1182C>T		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.00960 AC: 1461 AN: 152188 Hom.: 72 Cov.: 32

Gnomad AFR AF: 0.00603

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0778

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000768

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.00574

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

GnomAD4 genome AF: 0.00961 AC: 1463 AN: 152306 Hom.: 72 Cov.: 32 AF XY: 0.0118 AC XY: 880 AN XY: 74480

Gnomad4 AFR AF: 0.00606

Gnomad4 AMR AF: 0.0777

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000770

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000103

Gnomad4 OTH AF: 0.00568

Alfa AF: 0.000373 Hom.: 0

Bravo AF: 0.0134

Asia WGS AF: 0.00375 AC: 13 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.6
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: rs79285331; hg19: chr18-61145707;