dbSNP rs3744941: SERPINB5:c.-233T>C (chr18-63476820-T-C) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -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

Publications

9 publications found

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:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_002639.5, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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.

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.-233T>C		upstream_gene	N/A	NP_002630.2	P36952-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SERPINB5	ENST00000382771.9	TSL:1 MANE Select	c.-233T>C	upstream_gene	N/A	ENSP00000372221.4	P36952-1
SERPINB5	ENST00000489441.5	TSL:1	c.-233T>C	upstream_gene	N/A	ENSP00000467158.1	P36952-2
SERPINB5	ENST00000865015.1		c.-233T>C	upstream_gene	N/A	ENSP00000535074.1

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

African (AFR)

AF:

1.00

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.500

AC:

AN:

East Asian (EAS)

AF:

0.500

AC:

AN:

South Asian (SAS)

AF:

1.00

AC:

AN:

European-Finnish (FIN)

AF:

0.600

AC:

AN:

Middle Eastern (MID)

AF:

1.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.712

AC:

AN:

Other (OTH)

AF:

0.375

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.558

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.703

AC:

106631

AN:

151742

Hom.:

38147

Cov.:

AF XY:

0.696

AC XY:

51594

AN XY:

74142

show subpopulations

African (AFR)

AF:

0.846

AC:

35058

AN:

41420

American (AMR)

AF:

0.644

AC:

9833

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.626

AC:

2171

AN:

3468

East Asian (EAS)

AF:

0.618

AC:

3169

AN:

5126

South Asian (SAS)

AF:

0.633

AC:

3048

AN:

4816

European-Finnish (FIN)

AF:

0.593

AC:

6234

AN:

10508

Middle Eastern (MID)

AF:

0.718

AC:

211

AN:

294

European-Non Finnish (NFE)

AF:

0.661

AC:

44804

AN:

67830

Other (OTH)

AF:

0.692

AC:

1460

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1612

3224

4837

6449

8061

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

814

1628

2442

3256

4070

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.659

Hom.:

5017

Bravo

AF:

0.709

Asia WGS

AF:

0.663

AC:

2306

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.63

CADD

Benign

(source)

DANN

Benign

0.77

PhyloP100

-0.38

PromoterAI

0.20

Neutral

(source)

Mutation Taster

=299/1

polymorphism (auto)

(source)

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

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over