Variant 18-63902411-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_002575.3(SERPINB2):c.686G>A(p.Arg229His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0015 in 1,597,266 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.0020 ( 1 hom., cov: 33)

Exomes 𝑓: 0.0015 ( 6 hom. )

Consequence

SERPINB2
NM_002575.3 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.157

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]

SERPINB2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0041959584).

BP6

Variant 18-63902411-G-A is Benign according to our data. Variant chr18-63902411-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 728330.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAdExome4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
SERPINB2	NM_002575.3 linkuse as main transcript	c.686G>A	p.Arg229His	missense_variant	7/8	ENST00000299502.9	NP_002566.1
SERPINB2	NM_001143818.2 linkuse as main transcript	c.686G>A	p.Arg229His	missense_variant	8/9		NP_001137290.1
SERPINB2	XM_024451192.2 linkuse as main transcript	c.686G>A	p.Arg229His	missense_variant	7/8		XP_024306960.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
SERPINB2	ENST00000299502.9 linkuse as main transcript	c.686G>A	p.Arg229His	missense_variant	7/8	1	NM_002575.3	ENSP00000299502	P1
SERPINB2	ENST00000457692.5 linkuse as main transcript	c.686G>A	p.Arg229His	missense_variant	8/9	5		ENSP00000401645	P1
SERPINB2	ENST00000482254.1 linkuse as main transcript	n.642G>A		non_coding_transcript_exon_variant	6/6	5

Frequencies

GnomAD3 genomes

AF:

0.00197

AC:

299

AN:

152040

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000797

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000525

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00340

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00325

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.00143

AC:

344

AN:

240504

Hom.:

AF XY:

0.00137

AC XY:

178

AN XY:

130144

show subpopulations

Gnomad AFR exome

AF:

0.000760

Gnomad AMR exome

AF:

0.000378

Gnomad ASJ exome

AF:

0.000208

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00276

Gnomad NFE exome

AF:

0.00229

Gnomad OTH exome

AF:

0.00138

GnomAD4 exome

AF:

0.00146

AC:

2104

AN:

1445108

Hom.:

Cov.:

AF XY:

0.00152

AC XY:

1094

AN XY:

718106

show subpopulations

Gnomad4 AFR exome

AF:

0.000825

Gnomad4 AMR exome

AF:

0.000736

Gnomad4 ASJ exome

AF:

0.000118

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000240

Gnomad4 FIN exome

AF:

0.00347

Gnomad4 NFE exome

AF:

0.00163

Gnomad4 OTH exome

AF:

0.000989

GnomAD4 genome

AF:

0.00197

AC:

299

AN:

152158

Hom.:

Cov.:

AF XY:

0.00183

AC XY:

136

AN XY:

74374

show subpopulations

Gnomad4 AFR

AF:

0.000795

Gnomad4 AMR

AF:

0.000524

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00340

Gnomad4 NFE

AF:

0.00325

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.00280

Hom.:

Bravo

AF:

0.00129

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00186

AC:

ExAC

AF:

0.00137

AC:

166

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 02, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.062

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.43

CADD

Benign

7.6

DANN

Uncertain

0.99

DEOGEN2

Benign

0.16

T;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.066

LIST_S2

Benign

0.27

.;T

M_CAP

Benign

0.035

MetaRNN

Benign

0.0042

T;T

MetaSVM

Benign

-0.73

MutationAssessor

Benign

0.58

N;N

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.22

PROVEAN

Benign

-1.0

N;N

REVEL

Benign

0.082

Sift

Benign

0.20

T;T

Sift4G

Benign

0.12

T;T

Polyphen

0.038

B;B

Vest4

0.043

MVP

0.44

MPC

0.016

ClinPred

0.0026

GERP RS

1.2

Varity_R

0.058

gMVP

0.24

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

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