1-173477795-T-G

Variant names:

• chr1-173477795-T-G
• rs6671141
• NM_004905.3:c.95+303T>G

Variant summary

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

The NM_004905.3(PRDX6):​c.95+303T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.228 in 152,174 control chromosomes in the GnomAD database, including 4,279 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 0.23 (4279 hom., cov: 32)
• Consequence: PRDX6 NM_004905.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0310
• Publications: 5 publications found

Genes affected

PRDX6 (HGNC:16753): (peroxiredoxin 6) The protein encoded by this gene is a member of the thiol-specific antioxidant protein family. This protein is a bifunctional enzyme with two distinct active sites. It is involved in redox regulation of the cell; it can reduce H(2)O(2) and short chain organic, fatty acid, and phospholipid hydroperoxides. It may play a role in the regulation of phospholipid turnover as well as in protection against oxidative injury. [provided by RefSeq, Jul 2008]

PRDX6-AS1 (HGNC:54870): (PRDX6 antisense RNA 1)

TNFSF4 (HGNC:11934): (TNF superfamily member 4) This gene encodes a cytokine of the tumor necrosis factor (TNF) ligand family. The encoded protein functions in T cell antigen-presenting cell (APC) interactions and mediates adhesion of activated T cells to endothelial cells. Polymorphisms in this gene have been associated with Sjogren's syndrome and systemic lupus erythematosus. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2014]

TNFSF4 Gene-Disease associations (from GenCC):

• systemic lupus erythematosus

  Inheritance: Unknown Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.317 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004905.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRDX6	NM_004905.3	MANE Select	c.95+303T>G		intron	N/A	NP_004896.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRDX6	ENST00000340385.6	TSL:1 MANE Select	c.95+303T>G		intron	N/A	ENSP00000342026.5
	PRDX6	ENST00000460950.1	TSL:2	n.163+303T>G		intron	N/A
	PRDX6-AS1	ENST00000659863.1		n.250+25A>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.227 AC: 34589 AN: 152058 Hom.: 4264 Cov.: 32

Gnomad AFR AF: 0.321

Gnomad AMI AF: 0.218

Gnomad AMR AF: 0.196

Gnomad ASJ AF: 0.301

Gnomad EAS AF: 0.309

Gnomad SAS AF: 0.122

Gnomad FIN AF: 0.140

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.189

Gnomad OTH AF: 0.220

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

GnomAD4 genome AF: 0.228 AC: 34657 AN: 152174 Hom.: 4279 Cov.: 32 AF XY: 0.225 AC XY: 16730 AN XY: 74400

African (AFR) AF: 0.321 AC: 13342 AN: 41528

American (AMR) AF: 0.196 AC: 3000 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.301 AC: 1044 AN: 3468

East Asian (EAS) AF: 0.309 AC: 1592 AN: 5160

South Asian (SAS) AF: 0.122 AC: 590 AN: 4828

European-Finnish (FIN) AF: 0.140 AC: 1488 AN: 10600

Middle Eastern (MID) AF: 0.286 AC: 84 AN: 294

European-Non Finnish (NFE) AF: 0.189 AC: 12855 AN: 67988

Other (OTH) AF: 0.220 AC: 463 AN: 2108

Alfa AF: 0.211 Hom.: 562

Bravo AF: 0.238

Asia WGS AF: 0.226 AC: 784 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	8.9
DANN	Benign	0.67
PhyloP100		-0.031
PromoterAI		0.0094	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs6671141; hg19: chr1-173446934;