rs17883875

Variant names:

• chr14-64941396-G-C
• rs17883875
• NM_002083.4:c.222+1109C>G

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_002083.4(GPX2):​c.222+1109C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0105 in 1,284,550 control chromosomes in the GnomAD database, including 127 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 0.0084 (16 hom., cov: 32)
  • Exomes 𝑓: 0.011 (111 hom.)
• Consequence: GPX2 NM_002083.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0820
• Publications: 3 publications found

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:42960): (CHURC1-FNTB readthrough) This locus represents naturally occurring read-through transcription between the neighboring CHURC1 (churchill domain containing 1) and FNTB (farnesyltransferase, CAAX box, beta) on chromosome 14. The read-through transcript produces a fusion protein that shares sequence identity with each individual gene product. [provided by RefSeq, Feb 2011]

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

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BS2: High Homozygotes in GnomAd4 at 16 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPX2	NM_002083.4	c.222+1109C>G		intron_variant	Intron 1 of 1	ENST00000389614.6	NP_002074.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPX2	ENST00000389614.6	c.222+1109C>G		intron_variant	Intron 1 of 1	1	NM_002083.4	ENSP00000374265.5
CHURC1-FNTB	ENST00000549987.1	c.246+15316G>C		intron_variant	Intron 3 of 13	2		ENSP00000447121.2

Frequencies

GnomAD3 genomes AF: 0.00839 AC: 1277 AN: 152144 Hom.: 16 Cov.: 32

Gnomad AFR AF: 0.00193

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.00746

Gnomad ASJ AF: 0.00317

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00332

Gnomad FIN AF: 0.0108

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0136

Gnomad OTH AF: 0.00720

GnomAD4 exome AF: 0.0108 AC: 12215 AN: 1132288 Hom.: 111 Cov.: 30 AF XY: 0.0108 AC XY: 5995 AN XY: 555344

African (AFR) AF: 0.00132 AC: 32 AN: 24200

American (AMR) AF: 0.00429 AC: 120 AN: 27956

Ashkenazi Jewish (ASJ) AF: 0.00318 AC: 50 AN: 15742

East Asian (EAS) AF: 0.00 AC: 0 AN: 12598

South Asian (SAS) AF: 0.00547 AC: 415 AN: 75882

European-Finnish (FIN) AF: 0.0133 AC: 167 AN: 12570

Middle Eastern (MID) AF: 0.00487 AC: 15 AN: 3080

European-Non Finnish (NFE) AF: 0.0121 AC: 11083 AN: 919018

Other (OTH) AF: 0.00807 AC: 333 AN: 41242

GnomAD4 genome AF: 0.00839 AC: 1277 AN: 152262 Hom.: 16 Cov.: 32 AF XY: 0.00829 AC XY: 617 AN XY: 74468

African (AFR) AF: 0.00193 AC: 80 AN: 41540

American (AMR) AF: 0.00745 AC: 114 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00317 AC: 11 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5182

South Asian (SAS) AF: 0.00332 AC: 16 AN: 4822

European-Finnish (FIN) AF: 0.0108 AC: 115 AN: 10614

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

European-Non Finnish (NFE) AF: 0.0136 AC: 923 AN: 68024

Other (OTH) AF: 0.00712 AC: 15 AN: 2106

Alfa AF: 0.0127 Hom.: 5

Bravo AF: 0.00730

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	-0.85
CADD	Benign	3.7
DANN	Benign	0.50
PhyloP100		0.082
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs17883875; hg19: chr14-65408114;