rs440481

Positions:

• chr6-28531459-A-C
• chr6-28531459-A-T

Variant summary

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

The NM_001509.3(GPX5):​c.242-319A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.247 in 149,212 control chromosomes in the GnomAD database, including 5,465 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 0.25 (5465 hom., cov: 29)
• Consequence: GPX5 NM_001509.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0510

Genes affected

GPX5 (HGNC:4557): (glutathione peroxidase 5) This gene belongs to the glutathione peroxidase family. It is specifically expressed in the epididymis in the mammalian male reproductive tract, and is androgen-regulated. Unlike several other characterized glutathione peroxidases, this enzyme is not a selenoprotein, lacking the selenocysteine residue. Thus, it is selenium-independent, and has been proposed to play a role in protecting the membranes of spermatozoa from the damaging effects of lipid peroxidation and/or preventing premature acrosome reaction. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Oct 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• 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/exons	MANE	Protein	UniProt
GPX5	NM_001509.3	c.242-319A>C		intron_variant		ENST00000412168.7	NP_001500.1
GPX5	NM_003996.3	c.242-862A>C		intron_variant			NP_003987.2
GPX5	NR_144470.2	n.438-862A>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GPX5	ENST00000412168.7	c.242-319A>C		intron_variant		1	NM_001509.3	ENSP00000392398	P1
GPX5	ENST00000469384.1	c.242-862A>C		intron_variant		1		ENSP00000419935
GPX5	ENST00000442674.6	n.617-319A>C		intron_variant, non_coding_transcript_variant		5
GPX5	ENST00000483784.1	n.433-862A>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.247 AC: 36850 AN: 149098 Hom.: 5441 Cov.: 29

Gnomad AFR AF: 0.377

Gnomad AMI AF: 0.215

Gnomad AMR AF: 0.252

Gnomad ASJ AF: 0.184

Gnomad EAS AF: 0.489

Gnomad SAS AF: 0.327

Gnomad FIN AF: 0.162

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.162

Gnomad OTH AF: 0.238

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

GnomAD4 genome AF: 0.247 AC: 36929 AN: 149212 Hom.: 5465 Cov.: 29 AF XY: 0.250 AC XY: 18170 AN XY: 72800

Gnomad4 AFR AF: 0.377

Gnomad4 AMR AF: 0.252

Gnomad4 ASJ AF: 0.184

Gnomad4 EAS AF: 0.490

Gnomad4 SAS AF: 0.329

Gnomad4 FIN AF: 0.162

Gnomad4 NFE AF: 0.162

Gnomad4 OTH AF: 0.237

Alfa AF: 0.143 Hom.: 397

Bravo AF: 0.267

Asia WGS AF: 0.363 AC: 1262 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.4
DANN	Benign	0.13

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: rs440481; hg19: chr6-28499236;