rs11623705

Variant names:

• chr14-64939004-G-T
• rs11623705
• ENST00000549987.1:c.246+12924G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000549987.1(CHURC1-FNTB):​c.246+12924G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0906 in 156,886 control chromosomes in the GnomAD database, including 833 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 0.090 (799 hom., cov: 32)
  • Exomes 𝑓: 0.11 (34 hom.)
• Consequence: CHURC1-FNTB ENST00000549987.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.724
• Publications: 22 publications found

Genes affected

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]

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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.122 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPX2	NM_002083.4	c.*484C>A		downstream_gene_variant		ENST00000389614.6	NP_002074.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHURC1-FNTB	ENST00000549987.1	c.246+12924G>T		intron_variant	Intron 3 of 13	2		ENSP00000447121.2
GPX2	ENST00000389614.6	c.*484C>A		downstream_gene_variant		1	NM_002083.4	ENSP00000374265.5

Frequencies

GnomAD3 genomes AF: 0.0901 AC: 13701 AN: 152056 Hom.: 798 Cov.: 32

Gnomad AFR AF: 0.0228

Gnomad AMI AF: 0.133

Gnomad AMR AF: 0.0869

Gnomad ASJ AF: 0.0983

Gnomad EAS AF: 0.0718

Gnomad SAS AF: 0.0236

Gnomad FIN AF: 0.174

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.124

Gnomad OTH AF: 0.0755

GnomAD4 exome AF: 0.108 AC: 508 AN: 4712 Hom.: 34 AF XY: 0.101 AC XY: 241 AN XY: 2388

African (AFR) AF: 0.00 AC: 0 AN: 58

American (AMR) AF: 0.0802 AC: 73 AN: 910

Ashkenazi Jewish (ASJ) AF: 0.0577 AC: 3 AN: 52

East Asian (EAS) AF: 0.116 AC: 23 AN: 198

South Asian (SAS) AF: 0.0368 AC: 15 AN: 408

European-Finnish (FIN) AF: 0.171 AC: 26 AN: 152

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.125 AC: 345 AN: 2754

Other (OTH) AF: 0.128 AC: 23 AN: 180

GnomAD4 genome AF: 0.0901 AC: 13704 AN: 152174 Hom.: 799 Cov.: 32 AF XY: 0.0917 AC XY: 6823 AN XY: 74392

African (AFR) AF: 0.0227 AC: 944 AN: 41520

American (AMR) AF: 0.0871 AC: 1331 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0983 AC: 341 AN: 3470

East Asian (EAS) AF: 0.0720 AC: 373 AN: 5184

South Asian (SAS) AF: 0.0239 AC: 115 AN: 4818

European-Finnish (FIN) AF: 0.174 AC: 1844 AN: 10582

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.124 AC: 8450 AN: 67996

Other (OTH) AF: 0.0747 AC: 158 AN: 2114

Alfa AF: 0.109 Hom.: 1650

Bravo AF: 0.0825

Asia WGS AF: 0.0590 AC: 204 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	4.6
DANN	Benign	0.70
PhyloP100		0.72
Mutation Taster		=100/0	polymorphism (auto)

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: rs11623705; hg19: chr14-65405722;