rs1800669

chr14-64942486-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_002083.4(GPX2):c.222+19T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0253 in 1,604,084 control chromosomes in the GnomAD database, including 603 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 0.019 (37 hom., cov: 32)
  • Exomes 𝑓: 0.026 (566 hom.)
• Consequence: GPX2 NM_002083.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.193

Genes affected

GPX2 (HGNC:4554): (glutathione peroxidase 2) The protein encoded by this gene belongs to the glutathione peroxidase family, members of which catalyze the reduction of organic hydroperoxides and hydrogen peroxide (H2O2) by glutathione, and thereby protect cells against oxidative damage. Several isozymes of this gene family exist in vertebrates, which vary in cellular location and substrate specificity. This isozyme is predominantly expressed in the gastrointestinal tract (also in liver in human), is localized in the cytoplasm, and whose preferred substrate is hydrogen peroxide. Overexpression of this gene is associated with increased differentiation and proliferation in colorectal cancer. This isozyme is also a selenoprotein, containing the rare amino acid selenocysteine (Sec) at its active site. Sec is encoded by the UGA codon, which normally signals translation termination. The 3' UTRs of selenoprotein mRNAs contain a conserved stem-loop structure, designated the Sec insertion sequence (SECIS) element, that is necessary for the recognition of UGA as a Sec codon, rather than as a stop signal. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jul 2016]

CHURC1-FNTB (HGNC:):

CHURC1 (HGNC:20099): (churchill domain containing 1) Predicted to enable zinc ion binding activity. Predicted to be involved in positive regulation of transcription, DNA-templated. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0186 (2826/152264) while in subpopulation NFE AF= 0.0289 (1966/68010). AF 95% confidence interval is 0.0278. There are 37 homozygotes in gnomad4. There are 1359 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 38 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GPX2	NM_002083.4	c.222+19T>A		intron_variant		ENST00000389614.6
CHURC1-FNTB	NM_001202559.1	c.327+16406A>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GPX2	ENST00000389614.6	c.222+19T>A		intron_variant		1	NM_002083.4	P1

Frequencies

GnomAD3 genomes AF: 0.0186 AC: 2828 AN: 152146 Hom.: 38 Cov.: 32

Gnomad AFR AF: 0.00497

Gnomad AMI AF: 0.0252

Gnomad AMR AF: 0.0133

Gnomad ASJ AF: 0.0173

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00477

Gnomad FIN AF: 0.0298

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0289

Gnomad OTH AF: 0.0134

GnomAD3 exomes AF: 0.0185 AC: 4599 AN: 248564 Hom.: 64 AF XY: 0.0187 AC XY: 2522 AN XY: 134952

Gnomad AFR exome AF: 0.00368

Gnomad AMR exome AF: 0.00925

Gnomad ASJ exome AF: 0.0128

Gnomad EAS exome AF: 0.0000556

Gnomad SAS exome AF: 0.00611

Gnomad FIN exome AF: 0.0341

Gnomad NFE exome AF: 0.0272

Gnomad OTH exome AF: 0.0190

GnomAD4 exome AF: 0.0260 AC: 37798 AN: 1451820 Hom.: 566 Cov.: 29 AF XY: 0.0254 AC XY: 18366 AN XY: 722764

Gnomad4 AFR exome AF: 0.00357

Gnomad4 AMR exome AF: 0.00960

Gnomad4 ASJ exome AF: 0.0136

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00703

Gnomad4 FIN exome AF: 0.0337

Gnomad4 NFE exome AF: 0.0301

Gnomad4 OTH exome AF: 0.0208

GnomAD4 genome AF: 0.0186 AC: 2826 AN: 152264 Hom.: 37 Cov.: 32 AF XY: 0.0183 AC XY: 1359 AN XY: 74450

Gnomad4 AFR AF: 0.00491

Gnomad4 AMR AF: 0.0133

Gnomad4 ASJ AF: 0.0173

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00477

Gnomad4 FIN AF: 0.0298

Gnomad4 NFE AF: 0.0289

Gnomad4 OTH AF: 0.0132

Alfa AF: 0.0239 Hom.: 12

Bravo AF: 0.0168

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	1.4
Dann	Benign	0.55
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3

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: rs1800669; hg19: chr14-65409204;