X-23682576-A-G

Variant names:

• chrX-23682576-A-G
• rs795489
• NM_006406.2:c.730+50A>G

Variant summary

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

The NM_006406.2(PRDX4):​c.730+50A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.39 (6229 hom., 11416 hem., cov: 20)
  • Exomes 𝑓: 0.42 (56408 hom. 104516 hem.)
• Consequence: PRDX4 NM_006406.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.26
• Publications: 10 publications found

Genes affected

PRDX4 (HGNC:17169): (peroxiredoxin 4) The protein encoded by this gene is an antioxidant enzyme and belongs to the peroxiredoxin family. The protein is localized to the cytoplasm. Peroxidases of the peroxiredoxin family reduce hydrogen peroxide and alkyl hydroperoxides to water and alcohol with the use of reducing equivalents derived from thiol-containing donor molecules. This protein has been found to play a regulatory role in the activation of the transcription factor NF-kappaB. [provided by RefSeq, Jul 2008]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.473 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRDX4	NM_006406.2	c.730+50A>G		intron_variant	Intron 5 of 6	ENST00000379341.9	NP_006397.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRDX4	ENST00000379341.9	c.730+50A>G		intron_variant	Intron 5 of 6	1	NM_006406.2	ENSP00000368646.4
PRDX4	ENST00000439422.1	c.361+50A>G		intron_variant	Intron 3 of 5	3		ENSP00000413736.1

Frequencies

GnomAD3 genomes AF: 0.393 AC: 42067 AN: 107058 Hom.: 6233 Cov.: 20

Gnomad AFR AF: 0.311

Gnomad AMI AF: 0.405

Gnomad AMR AF: 0.463

Gnomad ASJ AF: 0.515

Gnomad EAS AF: 0.494

Gnomad SAS AF: 0.347

Gnomad FIN AF: 0.419

Gnomad MID AF: 0.498

Gnomad NFE AF: 0.412

Gnomad OTH AF: 0.422

GnomAD2 exomes AF: 0.430 AC: 53578 AN: 124571 AF XY: 0.423

Gnomad AFR exome AF: 0.312

Gnomad AMR exome AF: 0.543

Gnomad ASJ exome AF: 0.498

Gnomad EAS exome AF: 0.509

Gnomad FIN exome AF: 0.428

Gnomad NFE exome AF: 0.418

Gnomad OTH exome AF: 0.434

GnomAD4 exome AF: 0.421 AC: 372512 AN: 885835 Hom.: 56408 Cov.: 13 AF XY: 0.441 AC XY: 104516 AN XY: 237089

African (AFR) AF: 0.311 AC: 6203 AN: 19967

American (AMR) AF: 0.545 AC: 11329 AN: 20795

Ashkenazi Jewish (ASJ) AF: 0.515 AC: 7055 AN: 13688

East Asian (EAS) AF: 0.505 AC: 11209 AN: 22188

South Asian (SAS) AF: 0.361 AC: 13501 AN: 37422

European-Finnish (FIN) AF: 0.432 AC: 14096 AN: 32650

Middle Eastern (MID) AF: 0.481 AC: 1615 AN: 3361

European-Non Finnish (NFE) AF: 0.418 AC: 292177 AN: 699740

Other (OTH) AF: 0.425 AC: 15327 AN: 36024

GnomAD4 genome AF: 0.393 AC: 42076 AN: 107103 Hom.: 6229 Cov.: 20 AF XY: 0.386 AC XY: 11416 AN XY: 29611

African (AFR) AF: 0.311 AC: 9165 AN: 29485

American (AMR) AF: 0.463 AC: 4491 AN: 9692

Ashkenazi Jewish (ASJ) AF: 0.515 AC: 1339 AN: 2598

East Asian (EAS) AF: 0.493 AC: 1666 AN: 3382

South Asian (SAS) AF: 0.346 AC: 844 AN: 2440

European-Finnish (FIN) AF: 0.419 AC: 2154 AN: 5140

Middle Eastern (MID) AF: 0.519 AC: 110 AN: 212

European-Non Finnish (NFE) AF: 0.412 AC: 21429 AN: 52061

Other (OTH) AF: 0.426 AC: 615 AN: 1443

Alfa AF: 0.386 Hom.: 11199

Bravo AF: 0.400

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	6.1
DANN	Benign	0.50
PhyloP100		1.3
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: rs795489; hg19: chrX-23700693; COSMIC: COSV65025825; COSMIC: COSV65025825;