rs3130559

Positions:

• chr6-31129524-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0220

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: This place is a probable branch point but likely benign (scored 2 / 10). 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PSORS1C1	NM_014068.3	c.-64-45C>T		intron_variant		ENST00000259881.10	NP_054787.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PSORS1C1	ENST00000259881.10	c.-64-45C>T		intron_variant		1	NM_014068.3	ENSP00000259881.9

Frequencies

GnomAD3 genomes AF: 0.278 AC: 42275 AN: 151984 Hom.: 6294 Cov.: 32

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.: 0 AF XY: 0.234 AC XY: 76736 AN XY: 328364

Gnomad4 AFR exome AF: 0.375

Gnomad4 AMR exome AF: 0.319

Gnomad4 ASJ exome AF: 0.268

Gnomad4 EAS exome AF: 0.404

Gnomad4 SAS exome AF: 0.204

Gnomad4 FIN exome AF: 0.209

Gnomad4 NFE exome AF: 0.214

Gnomad4 OTH exome AF: 0.240

GnomAD4 genome AF: 0.278 AC: 42320 AN: 152102 Hom.: 6302 Cov.: 32 AF XY: 0.277 AC XY: 20620 AN XY: 74348

Gnomad4 AFR AF: 0.383

Gnomad4 AMR AF: 0.319

Gnomad4 ASJ AF: 0.259

Gnomad4 EAS AF: 0.388

Gnomad4 SAS AF: 0.235

Gnomad4 FIN AF: 0.205

Gnomad4 NFE AF: 0.216

Gnomad4 OTH AF: 0.264

Alfa AF: 0.226 Hom.: 8239

Bravo AF: 0.292

Asia WGS AF: 0.268 AC: 931 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	8.3
DANN	Benign	0.73
BranchPoint Hunter		2.0

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

Other links and lift over

dbSNP: rs3130559; hg19: chr6-31097301;