1-173478437-A-G

Variant names:

• chr1-173478437-A-G
• rs35918328
• NM_004905.3:c.95+945A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_004905.3(PRDX6):​c.95+945A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0142 in 151,890 control chromosomes in the GnomAD database, including 45 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 0.014 (45 hom., cov: 32)
• Consequence: PRDX6 NM_004905.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.19
• Publications: 1 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)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0142 (2158/151890) while in subpopulation AFR AF = 0.0494 (2046/41392). AF 95% confidence interval is 0.0476. There are 45 homozygotes in GnomAd4. There are 1013 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 45 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRDX6	NM_004905.3	c.95+945A>G		intron_variant	Intron 1 of 4	ENST00000340385.6	NP_004896.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRDX6	ENST00000340385.6	c.95+945A>G		intron_variant	Intron 1 of 4	1	NM_004905.3	ENSP00000342026.5

Frequencies

GnomAD3 genomes AF: 0.0142 AC: 2159 AN: 151806 Hom.: 45 Cov.: 32

Gnomad AFR AF: 0.0496

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00439

Gnomad ASJ AF: 0.000864

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00955

Gnomad NFE AF: 0.000309

Gnomad OTH AF: 0.00861

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

GnomAD4 genome AF: 0.0142 AC: 2158 AN: 151890 Hom.: 45 Cov.: 32 AF XY: 0.0137 AC XY: 1013 AN XY: 74210

African (AFR) AF: 0.0494 AC: 2046 AN: 41392

American (AMR) AF: 0.00438 AC: 67 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.000864 AC: 3 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.00 AC: 0 AN: 4808

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10462

Middle Eastern (MID) AF: 0.0103 AC: 3 AN: 290

European-Non Finnish (NFE) AF: 0.000309 AC: 21 AN: 67986

Other (OTH) AF: 0.00853 AC: 18 AN: 2110

Alfa AF: 0.00624 Hom.: 3

Bravo AF: 0.0162

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.83
DANN	Benign	0.69
PhyloP100		-2.2
Mutation Taster		=100/0	polymorphism

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: rs35918328; hg19: chr1-173447576;