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GeneBe

18-63902526-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_002575.3(SERPINB2):c.801G>A(p.Leu267=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00148 in 1,613,406 control chromosomes in the GnomAD database, including 60 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0028 ( 11 hom., cov: 33)
Exomes 𝑓: 0.0013 ( 49 hom. )

Consequence

SERPINB2
NM_002575.3 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.270
Variant links:
Genes affected
SERPINB2 (HGNC:8584): (serpin family B member 2) Predicted to enable serine-type endopeptidase inhibitor activity. Predicted to be involved in negative regulation of endopeptidase activity. Predicted to be located in extracellular region and plasma membrane. Predicted to be active in extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.58).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 18-63902526-G-A is Benign according to our data. Variant chr18-63902526-G-A is described in ClinVar as [Benign]. Clinvar id is 716695.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=0.27 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0617 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SERPINB2NM_002575.3 linkuse as main transcriptc.801G>A p.Leu267= synonymous_variant 7/8 ENST00000299502.9
SERPINB2NM_001143818.2 linkuse as main transcriptc.801G>A p.Leu267= synonymous_variant 8/9
SERPINB2XM_024451192.2 linkuse as main transcriptc.801G>A p.Leu267= synonymous_variant 7/8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SERPINB2ENST00000299502.9 linkuse as main transcriptc.801G>A p.Leu267= synonymous_variant 7/81 NM_002575.3 P1
SERPINB2ENST00000457692.5 linkuse as main transcriptc.801G>A p.Leu267= synonymous_variant 8/95 P1
SERPINB2ENST00000482254.1 linkuse as main transcriptn.757G>A non_coding_transcript_exon_variant 6/65

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00275
AC:
419
AN:
152152
Hom.:
11
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000917
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000327
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.0670
Gnomad SAS
AF:
0.00436
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.00287
GnomAD3 exomes
AF:
0.00476
AC:
1190
AN:
250186
Hom.:
42
AF XY:
0.00448
AC XY:
606
AN XY:
135268
show subpopulations
Gnomad AFR exome
AF:
0.00105
Gnomad AMR exome
AF:
0.0000584
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0609
Gnomad SAS exome
AF:
0.00111
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000530
Gnomad OTH exome
AF:
0.00280
GnomAD4 exome
AF:
0.00135
AC:
1970
AN:
1461136
Hom.:
49
Cov.:
31
AF XY:
0.00129
AC XY:
938
AN XY:
726852
show subpopulations
Gnomad4 AFR exome
AF:
0.000628
Gnomad4 AMR exome
AF:
0.000112
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0382
Gnomad4 SAS exome
AF:
0.00126
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000306
Gnomad4 OTH exome
AF:
0.00471
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00277
AC:
422
AN:
152270
Hom.:
11
Cov.:
33
AF XY:
0.00300
AC XY:
223
AN XY:
74440
show subpopulations
Gnomad4 AFR
AF:
0.000914
Gnomad4 AMR
AF:
0.000327
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.0676
Gnomad4 SAS
AF:
0.00415
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00378
Alfa
AF:
0.000423
Hom.:
0
Bravo
AF:
0.00269
Asia WGS
AF:
0.0290
AC:
102
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeDec 31, 2019- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.58
Cadd
Benign
7.8
Dann
Benign
0.76

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.070
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.

Other links and lift over

dbSNP: rs148240038; hg19: chr18-61569760; COSMIC: COSV55094380; COSMIC: COSV55094380; API