18-63480916-C-T

Variant names:

• chr18-63480916-C-T
• rs8089104
• NM_002639.5:c.-7-3506C>T

Variant summary

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

The NM_002639.5(SERPINB5):​c.-7-3506C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.501 in 152,056 control chromosomes in the GnomAD database, including 19,420 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 0.50 (19420 hom., cov: 32)
• Consequence: SERPINB5 NM_002639.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0170

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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.584 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SERPINB5	NM_002639.5	c.-7-3506C>T		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.-7-3506C>T		intron_variant	Intron 1 of 6	1	NM_002639.5	ENSP00000372221.4
SERPINB5	ENST00000489441.5	c.-7-3506C>T		intron_variant	Intron 1 of 4	1		ENSP00000467158.1
SERPINB5	ENST00000424602.1	c.-7-3506C>T		intron_variant	Intron 1 of 3	4		ENSP00000408821.1

Frequencies

GnomAD3 genomes AF: 0.501 AC: 76079 AN: 151938 Hom.: 19395 Cov.: 32

Gnomad AFR AF: 0.590

Gnomad AMI AF: 0.464

Gnomad AMR AF: 0.434

Gnomad ASJ AF: 0.429

Gnomad EAS AF: 0.518

Gnomad SAS AF: 0.494

Gnomad FIN AF: 0.432

Gnomad MID AF: 0.434

Gnomad NFE AF: 0.476

Gnomad OTH AF: 0.485

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

GnomAD4 genome AF: 0.501 AC: 76149 AN: 152056 Hom.: 19420 Cov.: 32 AF XY: 0.495 AC XY: 36807 AN XY: 74304

Gnomad4 AFR AF: 0.590

Gnomad4 AMR AF: 0.434

Gnomad4 ASJ AF: 0.429

Gnomad4 EAS AF: 0.518

Gnomad4 SAS AF: 0.494

Gnomad4 FIN AF: 0.432

Gnomad4 NFE AF: 0.476

Gnomad4 OTH AF: 0.487

Alfa AF: 0.479 Hom.: 3467

Bravo AF: 0.499

Asia WGS AF: 0.499 AC: 1738 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	4.3
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: rs8089104; hg19: chr18-61148149;