dbSNP rs3130559: PSORS1C1:c.-64-45C>T (chr6-31129524-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_014068.3(PSORS1C1):c.-64-45C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.246 in 754,822 control chromosomes in the GnomAD database, including 24,897 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.28 ( 6302 hom., cov: 32)

Exomes 𝑓: 0.24 ( 18595 hom. )

Consequence

PSORS1C1
NM_014068.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0220

Publications

55 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

This position, referring to a specific DNA site, is a probable branch point but is likely benign (scored 2 / 10, using the threshold of <=3). The score ranges from 0 to 10, with values ≤3 considered benign and >5 classified as pathogenic. Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.378 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014068.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PSORS1C1	NM_014068.3	MANE Select	c.-64-45C>T		intron	N/A	NP_054787.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
PSORS1C1	ENST00000259881.10	TSL:1 MANE Select	c.-64-45C>T	intron	N/A	ENSP00000259881.9
PSORS1C1	ENST00000479581.5	TSL:1	n.62-10117C>T	intron	N/A
PSORS1C1	ENST00000552747.1	TSL:1	n.54-8835C>T	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.278

AC:

42275

AN:

151984

Hom.:

6294

Cov.:

show subpopulations

Gnomad AFR

AF:

0.383

Gnomad AMI

AF:

0.0987

Gnomad AMR

AF:

0.318

Gnomad ASJ

AF:

0.259

Gnomad EAS

AF:

0.388

Gnomad SAS

AF:

0.234

Gnomad FIN

AF:

0.205

Gnomad MID

AF:

0.212

Gnomad NFE

AF:

0.216

Gnomad OTH

AF:

0.263

GnomAD4 exome

AF:

0.238

AC:

143556

AN:

602720

Hom.:

18595

Cov.:

AF XY:

0.234

AC XY:

76736

AN XY:

328364

show subpopulations

African (AFR)

AF:

0.375

AC:

6356

AN:

16970

American (AMR)

AF:

0.319

AC:

12829

AN:

40198

Ashkenazi Jewish (ASJ)

AF:

0.268

AC:

5061

AN:

18884

East Asian (EAS)

AF:

0.404

AC:

14483

AN:

35828

South Asian (SAS)

AF:

0.204

AC:

13400

AN:

65526

European-Finnish (FIN)

AF:

0.209

AC:

10498

AN:

50314

Middle Eastern (MID)

AF:

0.202

AC:

728

AN:

3610

European-Non Finnish (NFE)

AF:

0.214

AC:

72503

AN:

339378

Other (OTH)

AF:

0.240

AC:

7698

AN:

32012

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

5213

10427

15640

20854

26067

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

650

1300

1950

2600

3250

<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:

0.278

AC:

42320

AN:

152102

Hom.:

6302

Cov.:

AF XY:

0.277

AC XY:

20620

AN XY:

74348

show subpopulations

African (AFR)

AF:

0.383

AC:

15862

AN:

41462

American (AMR)

AF:

0.319

AC:

4869

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.259

AC:

899

AN:

3470

East Asian (EAS)

AF:

0.388

AC:

2005

AN:

5166

South Asian (SAS)

AF:

0.235

AC:

1132

AN:

4822

European-Finnish (FIN)

AF:

0.205

AC:

2174

AN:

10604

Middle Eastern (MID)

AF:

0.211

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.216

AC:

14670

AN:

67988

Other (OTH)

AF:

0.264

AC:

557

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1523

3046

4569

6092

7615

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

426

852

1278

1704

2130

<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:

0.238

Hom.:

20501

Bravo

AF:

0.292

Asia WGS

AF:

0.268

AC:

931

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

8.3

(source)

DANN

Benign

0.73

PhyloP100

-0.022

BranchPoint Hunter

2.0

Mutation Taster

=100/0

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over