rs2279244

Positions:

• chr12-75502884-C-T

Variant summary

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

The NM_006851.3(GLIPR1):​c.*3906C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.235 in 151,922 control chromosomes in the GnomAD database, including 4,448 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 0.24 (4448 hom., cov: 32)
  • Exomes 𝑓: 0.067 (0 hom.)
• Consequence: GLIPR1 NM_006851.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0570

Genes affected

GLIPR1 (HGNC:17001): (GLI pathogenesis related 1) This gene encodes a protein with similarity to both the pathogenesis-related protein (PR) superfamily and the cysteine-rich secretory protein (CRISP) family. Increased expression of this gene is associated with myelomocytic differentiation in macrophage and decreased expression of this gene through gene methylation is associated with prostate cancer. The protein has proapoptotic activities in prostate and bladder cancer cells. This gene is a member of a cluster on chromosome 12 containing two other similar genes. Alternatively spliced variants which encode different protein isoforms have been described; however, not all variants have been fully characterized. [provided by RefSeq, Jul 2008]

KRR1 (HGNC:5176): (KRR1 small subunit processome component homolog) Enables RNA binding activity. Predicted to be involved in rRNA processing. Located in chromosome; intercellular bridge; and nuclear lumen. [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=-0.78).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.304 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GLIPR1	NM_006851.3	c.*3906C>T		3_prime_UTR_variant	6/6	ENST00000266659.8
KRR1	NM_007043.7	c.832-884G>A		intron_variant		ENST00000229214.9
KRR1	XM_047428133.1	c.538-884G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GLIPR1	ENST00000266659.8	c.*3906C>T		3_prime_UTR_variant	6/6	1	NM_006851.3	P1
KRR1	ENST00000229214.9	c.832-884G>A		intron_variant		1	NM_007043.7	P1
KRR1	ENST00000438169.6	c.661-884G>A		intron_variant		1
KRR1	ENST00000551070.5	n.380-884G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.235 AC: 35683 AN: 151772 Hom.: 4440 Cov.: 32

Gnomad AFR AF: 0.208

Gnomad AMI AF: 0.100

Gnomad AMR AF: 0.292

Gnomad ASJ AF: 0.246

Gnomad EAS AF: 0.119

Gnomad SAS AF: 0.317

Gnomad FIN AF: 0.192

Gnomad MID AF: 0.325

Gnomad NFE AF: 0.249

Gnomad OTH AF: 0.268

GnomAD4 exome AF: 0.0667 AC: 2 AN: 30 Hom.: 0 Cov.: 0 AF XY: 0.111 AC XY: 2 AN XY: 18

Gnomad4 FIN exome AF: 0.0833

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.235 AC: 35710 AN: 151892 Hom.: 4448 Cov.: 32 AF XY: 0.234 AC XY: 17406 AN XY: 74254

Gnomad4 AFR AF: 0.208

Gnomad4 AMR AF: 0.293

Gnomad4 ASJ AF: 0.246

Gnomad4 EAS AF: 0.118

Gnomad4 SAS AF: 0.317

Gnomad4 FIN AF: 0.192

Gnomad4 NFE AF: 0.249

Gnomad4 OTH AF: 0.268

Alfa AF: 0.261 Hom.: 915

Bravo AF: 0.239

Asia WGS AF: 0.219 AC: 761 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	1.5
DANN	Benign	0.59

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: rs2279244; hg19: chr12-75896664;