rs3778638

Variant names:

• chr6-31124347-G-A
• rs3778638
• NM_014068.3:c.-228-1329G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014068.3(PSORS1C1):​c.-228-1329G>A 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 152,068 control chromosomes in the GnomAD database, including 2,312 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 (2312 hom., cov: 32)
• Consequence: PSORS1C1 NM_014068.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.35
• Publications: 32 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=-0.97).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.185 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PSORS1C1	NM_014068.3	c.-228-1329G>A		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.-228-1329G>A		intron_variant	Intron 1 of 5	1	NM_014068.3	ENSP00000259881.9

Frequencies

GnomAD3 genomes AF: 0.170 AC: 25848 AN: 151950 Hom.: 2311 Cov.: 32

Gnomad AFR AF: 0.136

Gnomad AMI AF: 0.154

Gnomad AMR AF: 0.173

Gnomad ASJ AF: 0.299

Gnomad EAS AF: 0.130

Gnomad SAS AF: 0.193

Gnomad FIN AF: 0.152

Gnomad MID AF: 0.188

Gnomad NFE AF: 0.188

Gnomad OTH AF: 0.182

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

GnomAD4 genome AF: 0.170 AC: 25856 AN: 152068 Hom.: 2312 Cov.: 32 AF XY: 0.170 AC XY: 12658 AN XY: 74340

African (AFR) AF: 0.136 AC: 5623 AN: 41468

American (AMR) AF: 0.172 AC: 2633 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.299 AC: 1038 AN: 3470

East Asian (EAS) AF: 0.130 AC: 672 AN: 5168

South Asian (SAS) AF: 0.194 AC: 933 AN: 4818

European-Finnish (FIN) AF: 0.152 AC: 1607 AN: 10560

Middle Eastern (MID) AF: 0.188 AC: 55 AN: 292

European-Non Finnish (NFE) AF: 0.188 AC: 12772 AN: 67984

Other (OTH) AF: 0.181 AC: 383 AN: 2112

Alfa AF: 0.184 Hom.: 11363

Bravo AF: 0.170

Asia WGS AF: 0.167 AC: 582 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.053
DANN	Benign	0.67
PhyloP100		-2.3
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: rs3778638; hg19: chr6-31092124;