rs4611

Positions:

• chr1-173487878-C-T

Variant summary

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

The NM_004905.3(PRDX6):​c.*15C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.267 in 1,611,100 control chromosomes in the GnomAD database, including 65,943 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 0.36 (12300 hom., cov: 32)
  • Exomes 𝑓: 0.26 (53643 hom.)
• Consequence: PRDX6 NM_004905.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.56

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)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.62 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRDX6	NM_004905.3	c.*15C>T		3_prime_UTR_variant	5/5	ENST00000340385.6	NP_004896.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRDX6	ENST00000340385.6	c.*15C>T		3_prime_UTR_variant	5/5	1	NM_004905.3	ENSP00000342026	P1
PRDX6-AS1	ENST00000669220.1	n.117+1413G>A		intron_variant, non_coding_transcript_variant
PRDX6	ENST00000470017.1	n.722C>T		non_coding_transcript_exon_variant	4/4	2

Frequencies

GnomAD3 genomes AF: 0.359 AC: 54573 AN: 152014 Hom.: 12247 Cov.: 32

Gnomad AFR AF: 0.626

Gnomad AMI AF: 0.284

Gnomad AMR AF: 0.256

Gnomad ASJ AF: 0.340

Gnomad EAS AF: 0.597

Gnomad SAS AF: 0.216

Gnomad FIN AF: 0.198

Gnomad MID AF: 0.294

Gnomad NFE AF: 0.240

Gnomad OTH AF: 0.317

GnomAD3 exomes AF: 0.284 AC: 71180 AN: 250328 Hom.: 12593 AF XY: 0.276 AC XY: 37330 AN XY: 135364

Gnomad AFR exome AF: 0.635

Gnomad AMR exome AF: 0.188

Gnomad ASJ exome AF: 0.329

Gnomad EAS exome AF: 0.615

Gnomad SAS exome AF: 0.212

Gnomad FIN exome AF: 0.200

Gnomad NFE exome AF: 0.242

Gnomad OTH exome AF: 0.271

GnomAD4 exome AF: 0.257 AC: 375251 AN: 1458968 Hom.: 53643 Cov.: 33 AF XY: 0.255 AC XY: 185246 AN XY: 725728

Gnomad4 AFR exome AF: 0.638

Gnomad4 AMR exome AF: 0.193

Gnomad4 ASJ exome AF: 0.329

Gnomad4 EAS exome AF: 0.575

Gnomad4 SAS exome AF: 0.213

Gnomad4 FIN exome AF: 0.200

Gnomad4 NFE exome AF: 0.240

Gnomad4 OTH exome AF: 0.286

GnomAD4 genome AF: 0.360 AC: 54696 AN: 152132 Hom.: 12300 Cov.: 32 AF XY: 0.355 AC XY: 26430 AN XY: 74388

Gnomad4 AFR AF: 0.627

Gnomad4 AMR AF: 0.256

Gnomad4 ASJ AF: 0.340

Gnomad4 EAS AF: 0.597

Gnomad4 SAS AF: 0.217

Gnomad4 FIN AF: 0.198

Gnomad4 NFE AF: 0.240

Gnomad4 OTH AF: 0.320

Alfa AF: 0.311 Hom.: 1652

Bravo AF: 0.378

Asia WGS AF: 0.432 AC: 1500 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.80
DANN	Benign	0.55

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

Publications

LitVar

Other links and lift over

dbSNP: rs4611; hg19: chr1-173457017; COSMIC: COSV61165110;