Variant chr18-63792405-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_003784.4(SERPINB7):c.181A>G(p.Asn61Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000276 in 1,604,008 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00032 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00027 ( 1 hom. )

Consequence

SERPINB7
NM_003784.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: 0.445

Variant links:

Genes affected

SERPINB7 (HGNC:13902): (serpin family B member 7) This gene encodes a member of a family of proteins which function as protease inhibitors. Expression of this gene is upregulated in IgA nephropathy and mutations have been found to cause palmoplantar keratoderma, Nagashima type. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2014]

SERPINB7 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008333504).

BP6

Variant 18-63792405-A-G is Benign according to our data. Variant chr18-63792405-A-G is described in ClinVar as [Benign]. Clinvar id is 2044929.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SERPINB7	NM_003784.4 linkuse as main transcript	c.181A>G	p.Asn61Asp	missense_variant	3/8	ENST00000398019.7	NP_003775.1	O75635-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SERPINB7	ENST00000398019.7 linkuse as main transcript	c.181A>G	p.Asn61Asp	missense_variant	3/8	1	NM_003784.4	ENSP00000381101.2		O75635-1

Frequencies

GnomAD3 genomes

AF:

0.000322

AC:

AN:

152186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00692

Gnomad SAS

AF:

0.00249

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000585

AC:

147

AN:

251218

Hom.:

AF XY:

0.000604

AC XY:

AN XY:

135798

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00626

Gnomad SAS exome

AF:

0.00105

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000271

AC:

393

AN:

1451704

Hom.:

Cov.:

AF XY:

0.000292

AC XY:

211

AN XY:

723012

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00649

Gnomad4 SAS exome

AF:

0.00124

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.07e-7

Gnomad4 OTH exome

AF:

0.000466

GnomAD4 genome

AF:

0.000322

AC:

AN:

152304

Hom.:

Cov.:

AF XY:

0.000363

AC XY:

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00694

Gnomad4 SAS

AF:

0.00249

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000515

Hom.:

Bravo

AF:

0.000400

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ExAC

AF:

0.000511

AC:

Asia WGS

AF:

0.00375

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Nov 27, 2023

- -

SERPINB7-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 18, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.078

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.48

CADD

Benign

7.7

DANN

Benign

0.45

DEOGEN2

Benign

0.043

.;T;T;.;T;T

Eigen

Benign

-0.69

Eigen_PC

Benign

-0.80

FATHMM_MKL

Benign

0.045

LIST_S2

Benign

0.44

T;T;.;T;.;T

M_CAP

Benign

0.017

MetaRNN

Benign

0.0083

T;T;T;T;T;T

MetaSVM

Benign

-0.66

MutationAssessor

Benign

1.4

.;L;L;.;L;.

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Uncertain

0.49

PROVEAN

Benign

0.86

N;N;N;N;N;N

REVEL

Benign

0.10

Sift

Benign

0.99

T;T;T;T;T;T

Sift4G

Benign

0.55

T;T;T;T;T;T

Polyphen

0.61

.;P;P;.;P;.

Vest4

0.20, 0.20

MVP

0.46

MPC

0.046

ClinPred

0.064

GERP RS

0.89

Varity_R

0.094

gMVP

0.061

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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