Genetic Variant SERPINB5:c.-233T>C (chr18-63476820-T-C) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_002639.5(SERPINB5):c.-233T>C variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.703 in 151,842 control chromosomes in the GnomAD database, including 38,170 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.70 ( 38147 hom., cov: 33)

Exomes 𝑓: 0.67 ( 23 hom. )

Consequence

SERPINB5
NM_002639.5 upstream_gene

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.376

Variant links:

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]

SERPINB5 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.63).

BP6

Variant 18-63476820-T-C is Benign according to our data. Variant chr18-63476820-T-C is described in ClinVar as [Benign]. Clinvar id is 1237193.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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 rank	MANE	Protein	UniProt
SERPINB5	NM_002639.5 link	c.-233T>C		upstream_gene_variant		ENST00000382771.9	NP_002630.2	P36952-1A0A024R2B6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SERPINB5	ENST00000382771.9 link	c.-233T>C		upstream_gene_variant		1	NM_002639.5	ENSP00000372221.4		P36952-1
SERPINB5	ENST00000489441.5 link	c.-233T>C		upstream_gene_variant		1		ENSP00000467158.1		P36952-2

Frequencies

GnomAD3 genomes

AF:

0.703

AC:

106523

AN:

151624

Hom.:

38097

Cov.:

show subpopulations

Gnomad AFR

AF:

0.846

Gnomad AMI

AF:

0.710

Gnomad AMR

AF:

0.645

Gnomad ASJ

AF:

0.626

Gnomad EAS

AF:

0.618

Gnomad SAS

AF:

0.633

Gnomad FIN

AF:

0.593

Gnomad MID

AF:

0.693

Gnomad NFE

AF:

0.661

Gnomad OTH

AF:

0.689

GnomAD4 exome

AF:

0.670

AC:

AN:

100

Hom.:

Cov.:

AF XY:

0.659

AC XY:

AN XY:

show subpopulations

Gnomad4 AFR exome

AF:

1.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.500

Gnomad4 EAS exome

AF:

0.500

Gnomad4 SAS exome

AF:

1.00

Gnomad4 FIN exome

AF:

0.600

Gnomad4 NFE exome

AF:

0.712

Gnomad4 OTH exome

AF:

0.375

GnomAD4 genome

AF:

0.703

AC:

106631

AN:

151742

Hom.:

38147

Cov.:

AF XY:

0.696

AC XY:

51594

AN XY:

74142

show subpopulations

Gnomad4 AFR

AF:

0.846

Gnomad4 AMR

AF:

0.644

Gnomad4 ASJ

AF:

0.626

Gnomad4 EAS

AF:

0.618

Gnomad4 SAS

AF:

0.633

Gnomad4 FIN

AF:

0.593

Gnomad4 NFE

AF:

0.661

Gnomad4 OTH

AF:

0.692

Alfa

AF:

0.443

Hom.:

500

Bravo

AF:

0.709

Asia WGS

AF:

0.663

AC:

2306

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jan 29, 2020

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.63

CADD

Benign

DANN

Benign

0.77

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over