18-63793161-T-C

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6

The NM_003784.4(SERPINB7):c.220T>C(p.Ser74Pro) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000426 in 1,501,686 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 19/24 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000040 ( 0 hom. )

Consequence

SERPINB7
NM_003784.4 missense, splice_region

Scores

Splicing: ADA: 0.00007150

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: -0.656

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

palmoplantar keratoderma, Nagashima type
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, PanelApp Australia, Labcorp Genetics (formerly Invitae), G2P, Orphanet

SERPINB7 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.030486435).

BP6

Variant 18-63793161-T-C is Benign according to our data. Variant chr18-63793161-T-C is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 2186287.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003784.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SERPINB7	NM_003784.4	MANE Select	c.220T>C	p.Ser74Pro	missense splice_region	Exon 4 of 8	NP_003775.1	O75635-1
SERPINB7	NM_001040147.3		c.220T>C	p.Ser74Pro	missense splice_region	Exon 4 of 8	NP_001035237.1	O75635-1
SERPINB7	NM_001261830.2		c.220T>C	p.Ser74Pro	missense splice_region	Exon 4 of 8	NP_001248759.1	O75635-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SERPINB7	ENST00000398019.7	TSL:1 MANE Select	c.220T>C	p.Ser74Pro	missense splice_region	Exon 4 of 8	ENSP00000381101.2	O75635-1
SERPINB7	ENST00000336429.6	TSL:1	c.220T>C	p.Ser74Pro	missense splice_region	Exon 4 of 8	ENSP00000337212.2	O75635-1
SERPINB7	ENST00000546027.5	TSL:2	c.220T>C	p.Ser74Pro	missense splice_region	Exon 4 of 8	ENSP00000444861.1	O75635-1

Frequencies

GnomAD3 genomes

AF:

0.0000657

AC:

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000317

AC:

AN:

220578

AF XY:

0.0000585

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000666

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000400

AC:

AN:

1349488

Hom.:

Cov.:

AF XY:

0.0000401

AC XY:

AN XY:

673352

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30112

American (AMR)

AF:

0.00

AC:

AN:

36436

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23772

East Asian (EAS)

AF:

0.00

AC:

AN:

37954

South Asian (SAS)

AF:

0.00

AC:

AN:

74420

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51846

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5380

European-Non Finnish (NFE)

AF:

0.0000503

AC:

AN:

1033770

Other (OTH)

AF:

0.0000358

AC:

AN:

55798

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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:

0.0000657

AC:

AN:

152198

Hom.:

Cov.:

AF XY:

0.0000672

AC XY:

AN XY:

74372

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41454

American (AMR)

AF:

0.000196

AC:

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5196

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000103

AC:

AN:

68032

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000416

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000412

AC:

ClinVar

ClinVar submissions

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

Inborn genetic diseases (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.077

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.41

CADD

Benign

1.9

(source)

DANN

Benign

0.31

DEOGEN2

Benign

0.062

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.0026

LIST_S2

Benign

0.15

M_CAP

Benign

0.0081

MetaRNN

Benign

0.030

MetaSVM

Benign

-0.92

MutationAssessor

Benign

-0.73

PhyloP100

-0.66

PrimateAI

Benign

0.27

PROVEAN

Benign

-0.99

REVEL

Benign

0.23

Sift

Benign

0.47

Sift4G

Benign

0.31

Polyphen

0.0

Vest4

0.14

MVP

0.24

MPC

0.022

ClinPred

0.042

GERP RS

0.29

Varity_R

0.10

gMVP

0.30

Mutation Taster

=99/1

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000071

dbscSNV1_RF

Benign

0.028

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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