6-31138400-T-C

Variant names:

• chr6-31138400-T-C
• rs1265098
• NM_014068.3:c.14-30T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 35 publications found

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

Our verdict: Benign. The variant received -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.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PSORS1C1	NM_014068.3	MANE Select	c.14-30T>C		intron	N/A	NP_054787.2	Q9UIG5-1
	PSORS1C2	NM_014069.3	MANE Select	c.56-94A>G		intron	N/A	NP_054788.2	Q9UIG4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PSORS1C1	ENST00000259881.10	TSL:1 MANE Select	c.14-30T>C		intron	N/A	ENSP00000259881.9	Q9UIG5-1
	PSORS1C2	ENST00000259845.5	TSL:1 MANE Select	c.56-94A>G		intron	N/A	ENSP00000259845.4	Q9UIG4
	PSORS1C1	ENST00000552747.1	TSL:1	n.95T>C		non_coding_transcript_exon	Exon 2 of 2

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

GnomAD2 exomes AF: 0.225 AC: 55445 AN: 246404 AF XY: 0.220

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 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

African (AFR) AF: 0.169 AC: 5661 AN: 33454

American (AMR) AF: 0.251 AC: 11233 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.0944 AC: 2466 AN: 26126

East Asian (EAS) AF: 0.119 AC: 4742 AN: 39690

South Asian (SAS) AF: 0.139 AC: 11962 AN: 86232

European-Finnish (FIN) AF: 0.338 AC: 17654 AN: 52302

Middle Eastern (MID) AF: 0.137 AC: 792 AN: 5764

European-Non Finnish (NFE) AF: 0.245 AC: 271799 AN: 1110252

Other (OTH) AF: 0.201 AC: 12123 AN: 60316

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

African (AFR) AF: 0.167 AC: 6857 AN: 41030

American (AMR) AF: 0.226 AC: 3430 AN: 15158

Ashkenazi Jewish (ASJ) AF: 0.100 AC: 347 AN: 3466

East Asian (EAS) AF: 0.152 AC: 773 AN: 5086

South Asian (SAS) AF: 0.146 AC: 691 AN: 4742

European-Finnish (FIN) AF: 0.344 AC: 3556 AN: 10346

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.243 AC: 16411 AN: 67614

Other (OTH) AF: 0.191 AC: 400 AN: 2092

Alfa AF: 0.226 Hom.: 6478

Bravo AF: 0.208

Asia WGS AF: 0.162 AC: 563 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	6.4
DANN	Benign	0.36
PhyloP100		0.32
PromoterAI		0.16	Neutral
Mutation Taster		=295/5	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1265098; hg19: chr6-31106177; COSMIC: COSV52535316; COSMIC: COSV52535316;