dbSNP rs1265096: PSORS1C1:p.Glu34Lys (chr6-31138712-G-A) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_014068.3(PSORS1C1):c.100G>A(p.Glu34Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0578 in 1,603,722 control chromosomes in the GnomAD database, including 3,521 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 Benign (no stars).

Frequency

Genomes: 𝑓 0.048 ( 251 hom., cov: 31)

Exomes 𝑓: 0.059 ( 3270 hom. )

Consequence

PSORS1C1
NM_014068.3 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -2.02

Publications

23 publications found

Variant links:

Genes affected

PSORS1C1 (HGNC:17202): (psoriasis susceptibility 1 candidate 1) This gene is one of several genes thought to confer susceptibility to psoriasis and systemic sclerosis, located on chromosome 6 near the major histocompatibility complex (MHC) class I region. [provided by RefSeq, Sep 2011]

PSORS1C1 links:

PSORS1C2 (HGNC:17199): (psoriasis susceptibility 1 candidate 2) Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

PSORS1C2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0018762052).

BP6

Variant 6-31138712-G-A is Benign according to our data. Variant chr6-31138712-G-A is described in ClinVar as Benign. ClinVar VariationId is 3056342.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0725 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PSORS1C1	NM_014068.3 link	c.100G>A	p.Glu34Lys	missense_variant	Exon 5 of 6	ENST00000259881.10	NP_054787.2	Q9UIG5-1D2IYL0
PSORS1C2	NM_014069.3 link	c.55+260C>T		intron_variant	Intron 1 of 1	ENST00000259845.5	NP_054788.2	Q9UIG4A0A1U9X9A6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PSORS1C1	ENST00000259881.10 link	c.100G>A	p.Glu34Lys	missense_variant	Exon 5 of 6	1	NM_014068.3	ENSP00000259881.9		Q9UIG5-1
PSORS1C2	ENST00000259845.5 link	c.55+260C>T		intron_variant	Intron 1 of 1	1	NM_014069.3	ENSP00000259845.4		Q9UIG4

Frequencies

GnomAD3 genomes

AF:

0.0481

AC:

6828

AN:

141910

Hom.:

251

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0138

Gnomad AMI

AF:

0.0489

Gnomad AMR

AF:

0.0161

Gnomad ASJ

AF:

0.00766

Gnomad EAS

AF:

0.000199

Gnomad SAS

AF:

0.00513

Gnomad FIN

AF:

0.117

Gnomad MID

AF:

0.00709

Gnomad NFE

AF:

0.0742

Gnomad OTH

AF:

0.0240

GnomAD2 exomes

AF:

0.0467

AC:

11534

AN:

246924

AF XY:

0.0466

show subpopulations

Gnomad AFR exome

AF:

0.0116

Gnomad AMR exome

AF:

0.00734

Gnomad ASJ exome

AF:

0.00432

Gnomad EAS exome

AF:

0.0000546

Gnomad FIN exome

AF:

0.113

Gnomad NFE exome

AF:

0.0742

Gnomad OTH exome

AF:

0.0394

GnomAD4 exome

AF:

0.0587

AC:

85875

AN:

1461708

Hom.:

3270

Cov.:

AF XY:

0.0570

AC XY:

41420

AN XY:

727160

show subpopulations

African (AFR)

AF:

0.00905

AC:

303

AN:

33480

American (AMR)

AF:

0.00778

AC:

348

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.00494

AC:

129

AN:

26134

East Asian (EAS)

AF:

0.000126

AC:

AN:

39700

South Asian (SAS)

AF:

0.00452

AC:

390

AN:

86258

European-Finnish (FIN)

AF:

0.110

AC:

5853

AN:

53272

Middle Eastern (MID)

AF:

0.00329

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0686

AC:

76331

AN:

1111984

Other (OTH)

AF:

0.0413

AC:

2497

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

4643

9286

13930

18573

23216

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2680

5360

8040

10720

13400

<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:

0.0481

AC:

6827

AN:

142014

Hom.:

251

Cov.:

AF XY:

0.0476

AC XY:

3297

AN XY:

69256

show subpopulations

African (AFR)

AF:

0.0138

AC:

525

AN:

38164

American (AMR)

AF:

0.0161

AC:

225

AN:

13978

Ashkenazi Jewish (ASJ)

AF:

0.00766

AC:

AN:

3002

East Asian (EAS)

AF:

0.000200

AC:

AN:

5012

South Asian (SAS)

AF:

0.00492

AC:

AN:

4472

European-Finnish (FIN)

AF:

0.117

AC:

1147

AN:

9778

Middle Eastern (MID)

AF:

0.00763

AC:

AN:

262

European-Non Finnish (NFE)

AF:

0.0742

AC:

4796

AN:

64614

Other (OTH)

AF:

0.0238

AC:

AN:

1894

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

302

604

905

1207

1509

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

172

258

344

430

<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:

0.0540

Hom.:

943

Bravo

AF:

0.0365

TwinsUK

AF:

0.0787

AC:

292

ALSPAC

AF:

0.0729

AC:

281

ESP6500AA

AF:

0.0165

AC:

ESP6500EA

AF:

0.0666

AC:

361

ExAC

AF:

0.0507

AC:

6108

Asia WGS

AF:

0.00404

AC:

AN:

3478

EpiCase

AF:

0.0528

EpiControl

AF:

0.0521

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

PSORS1C1-related disorder

Benign:1

Oct 21, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as 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

0.15

BayesDel_addAF

Benign

-0.78

BayesDel_noAF

Benign

-0.82

CADD

Benign

7.5

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.0022

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.010

MetaRNN

Benign

0.0019

MetaSVM

Benign

-0.93

MutationAssessor

Benign

0.0

PhyloP100

-2.0

PrimateAI

Benign

0.26

PROVEAN

Benign

-1.4

REVEL

Benign

0.10

Sift

Benign

0.33

Sift4G

Pathogenic

0.0

Polyphen

0.84

Vest4

0.054

MPC

0.84

ClinPred

0.0052

GERP RS

0.35

PromoterAI

-0.0039

Neutral

(source)

Varity_R

0.022

gMVP

0.072

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over