6-31138400-T-C

Position:

• chr6-31138400-T-C

Variant summary

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

The NM_014068.3(PSORS1C1):​c.14-30T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.231 in 1,609,584 control chromosomes in the GnomAD database, including 45,396 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.

• Frequency:
  • Genomes: 𝑓 0.22 (3788 hom., cov: 27)
  • Exomes 𝑓: 0.23 (41608 hom.)
• Consequence: PSORS1C1 NM_014068.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.321

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]

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

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.24 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PSORS1C1	NM_014068.3	c.14-30T>C		intron_variant		ENST00000259881.10
PSORS1C2	NM_014069.3	c.56-94A>G		intron_variant		ENST00000259845.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PSORS1C2	ENST00000259845.5	c.56-94A>G		intron_variant		1	NM_014069.3	P1
PSORS1C1	ENST00000259881.10	c.14-30T>C		intron_variant		1	NM_014068.3	P2

Frequencies

GnomAD3 genomes AF: 0.217 AC: 32727 AN: 150622 Hom.: 3781 Cov.: 27

Gnomad AFR AF: 0.167

Gnomad AMI AF: 0.270

Gnomad AMR AF: 0.226

Gnomad ASJ AF: 0.100

Gnomad EAS AF: 0.152

Gnomad SAS AF: 0.146

Gnomad FIN AF: 0.344

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.243

Gnomad OTH AF: 0.190

GnomAD3 exomes AF: 0.225 AC: 55445 AN: 246404 Hom.: 6985 AF XY: 0.220 AC XY: 29492 AN XY: 134338

Gnomad AFR exome AF: 0.172

Gnomad AMR exome AF: 0.255

Gnomad ASJ exome AF: 0.0875

Gnomad EAS exome AF: 0.170

Gnomad SAS exome AF: 0.143

Gnomad FIN exome AF: 0.347

Gnomad NFE exome AF: 0.244

Gnomad OTH exome AF: 0.217

GnomAD4 exome AF: 0.232 AC: 338432 AN: 1458850 Hom.: 41608 Cov.: 39 AF XY: 0.228 AC XY: 165249 AN XY: 725882

Gnomad4 AFR exome AF: 0.169

Gnomad4 AMR exome AF: 0.251

Gnomad4 ASJ exome AF: 0.0944

Gnomad4 EAS exome AF: 0.119

Gnomad4 SAS exome AF: 0.139

Gnomad4 FIN exome AF: 0.338

Gnomad4 NFE exome AF: 0.245

Gnomad4 OTH exome AF: 0.201

GnomAD4 genome AF: 0.217 AC: 32748 AN: 150734 Hom.: 3788 Cov.: 27 AF XY: 0.220 AC XY: 16159 AN XY: 73608

Gnomad4 AFR AF: 0.167

Gnomad4 AMR AF: 0.226

Gnomad4 ASJ AF: 0.100

Gnomad4 EAS AF: 0.152

Gnomad4 SAS AF: 0.146

Gnomad4 FIN AF: 0.344

Gnomad4 NFE AF: 0.243

Gnomad4 OTH AF: 0.191

Alfa AF: 0.222 Hom.: 3494

Bravo AF: 0.208

Asia WGS AF: 0.162 AC: 563 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	6.4
DANN	Benign	0.36

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1265098; hg19: chr6-31106177; COSMIC: COSV52535316; COSMIC: COSV52535316;