NM_014068.3:c.-228-3858G>C

Variant names:

• chr6-31121818-G-C
• rs2284177
• NM_014068.3:c.-228-3858G>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.-228-3858G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.17 in 152,258 control chromosomes in the GnomAD database, including 2,462 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 0.17 (2462 hom., cov: 34)
• Consequence: PSORS1C1 NM_014068.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0250
• Publications: 6 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]

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 (SAS) allele frequency at 95% confidence interval = 0.316 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PSORS1C1	NM_014068.3	c.-228-3858G>C		intron_variant	Intron 1 of 5	ENST00000259881.10	NP_054787.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PSORS1C1	ENST00000259881.10	c.-228-3858G>C		intron_variant	Intron 1 of 5	1	NM_014068.3	ENSP00000259881.9

Frequencies

GnomAD3 genomes AF: 0.170 AC: 25903 AN: 152140 Hom.: 2466 Cov.: 34

Gnomad AFR AF: 0.107

Gnomad AMI AF: 0.0800

Gnomad AMR AF: 0.206

Gnomad ASJ AF: 0.296

Gnomad EAS AF: 0.187

Gnomad SAS AF: 0.330

Gnomad FIN AF: 0.196

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.178

Gnomad OTH AF: 0.186

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.170 AC: 25896 AN: 152258 Hom.: 2462 Cov.: 34 AF XY: 0.176 AC XY: 13112 AN XY: 74446

African (AFR) AF: 0.107 AC: 4439 AN: 41556

American (AMR) AF: 0.206 AC: 3146 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.296 AC: 1028 AN: 3470

East Asian (EAS) AF: 0.187 AC: 971 AN: 5182

South Asian (SAS) AF: 0.330 AC: 1591 AN: 4824

European-Finnish (FIN) AF: 0.196 AC: 2080 AN: 10594

Middle Eastern (MID) AF: 0.265 AC: 78 AN: 294

European-Non Finnish (NFE) AF: 0.178 AC: 12097 AN: 68014

Other (OTH) AF: 0.186 AC: 393 AN: 2114

Alfa AF: 0.0894 Hom.: 157

Bravo AF: 0.165

Asia WGS AF: 0.279 AC: 970 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	1.5
DANN	Benign	0.44
PhyloP100		0.025
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2284177; hg19: chr6-31089595;