1-173481318-C-G

Variant names:

• chr1-173481318-C-G
• rs35052032
• NM_004905.3:c.96-8C>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_004905.3(PRDX6):​c.96-8C>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00175 in 1,608,984 control chromosomes in the GnomAD database, including 49 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0095 (27 hom., cov: 32)
  • Exomes 𝑓: 0.00094 (22 hom.)
• Consequence: PRDX6 NM_004905.3 splice_region, intron
• Scores: Splicing: ADA: 0.0004480
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.932
• Publications: 0 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BP6: Variant 1-173481318-C-G is Benign according to our data. Variant chr1-173481318-C-G is described in ClinVar as Benign. ClinVar VariationId is 767728.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00951 (1448/152258) while in subpopulation AFR AF = 0.0335 (1390/41538). AF 95% confidence interval is 0.032. There are 27 homozygotes in GnomAd4. There are 653 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 27 AR gene

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRDX6	NM_004905.3	MANE Select	c.96-8C>G		splice_region intron	N/A	NP_004896.1	P30041

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRDX6	ENST00000340385.6	TSL:1 MANE Select	c.96-8C>G		splice_region intron	N/A	ENSP00000342026.5	P30041
	PRDX6	ENST00000922555.1		c.162-8C>G		splice_region intron	N/A	ENSP00000592614.1
	PRDX6	ENST00000867927.1		c.96-8C>G		splice_region intron	N/A	ENSP00000537986.1

Frequencies

GnomAD3 genomes AF: 0.00947 AC: 1441 AN: 152140 Hom.: 27 Cov.: 32

Gnomad AFR AF: 0.0334

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00249

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00766

GnomAD2 exomes AF: 0.00260 AC: 645 AN: 248372 AF XY: 0.00193

Gnomad AFR exome AF: 0.0366

Gnomad AMR exome AF: 0.00121

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000267

Gnomad OTH exome AF: 0.000825

GnomAD4 exome AF: 0.000943 AC: 1374 AN: 1456726 Hom.: 22 Cov.: 30 AF XY: 0.000818 AC XY: 593 AN XY: 724630

African (AFR) AF: 0.0345 AC: 1147 AN: 33206

American (AMR) AF: 0.00138 AC: 61 AN: 44062

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25988

East Asian (EAS) AF: 0.00 AC: 0 AN: 39640

South Asian (SAS) AF: 0.0000350 AC: 3 AN: 85712

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53396

Middle Eastern (MID) AF: 0.000872 AC: 5 AN: 5734

European-Non Finnish (NFE) AF: 0.0000370 AC: 41 AN: 1108802

Other (OTH) AF: 0.00194 AC: 117 AN: 60186

GnomAD4 genome AF: 0.00951 AC: 1448 AN: 152258 Hom.: 27 Cov.: 32 AF XY: 0.00877 AC XY: 653 AN XY: 74438

African (AFR) AF: 0.0335 AC: 1390 AN: 41538

American (AMR) AF: 0.00248 AC: 38 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68006

Other (OTH) AF: 0.00758 AC: 16 AN: 2112

Alfa AF: 0.00332 Hom.: 1

Bravo AF: 0.0105

Asia WGS AF: 0.00115 AC: 4 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	9.9
DANN	Benign	0.70
PhyloP100		-0.93
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.1
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00045
dbscSNV1_RF	Benign	0.044
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: rs35052032; hg19: chr1-173450457;