rs2281836

chr14-49598999-G-Cchr14-49598999-G-T

Variant summary

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

The NM_152329.4(LRR1):c.-22G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.713 in 1,591,264 control chromosomes in the GnomAD database, including 415,078 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 0.71 (39507 hom., cov: 36)
  • Exomes 𝑓: 0.71 (375571 hom.)
• Consequence: LRR1 NM_152329.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.880

Genes affected

LRR1 (HGNC:19742): (leucine rich repeat protein 1) The protein encoded by this gene contains a leucine-rich repeat (LRR). It specifically interacts with TNFRSF9/4-1BB, a member of the tumor necrosis factor receptor (TNFR) superfamily. Overexpression of this gene suppresses the activation of NF-kappa B induced by TNFRSF9 or TNF receptor-associated factor 2 (TRAF2), which suggests that this protein is a negative regulator of TNFRSF9-mediated signaling cascades. Alternative splicing results in multiple transcript variants.[provided by RefSeq, Feb 2011]

RPS29 (HGNC:10419): (ribosomal protein S29) Ribosomes, the organelles that catalyze protein synthesis, consist of a small 40S subunit and a large 60S subunit. Together these subunits are composed of 4 RNA species and approximately 80 structurally distinct proteins. This gene encodes a ribosomal protein that is a component of the 40S subunit and a member of the S14P family of ribosomal proteins. The protein, which contains a C2-C2 zinc finger-like domain that can bind to zinc, can enhance the tumor suppressor activity of Ras-related protein 1A (KREV1). It is located in the cytoplasm. Variable expression of this gene in colorectal cancers compared to adjacent normal tissues has been observed, although no correlation between the level of expression and the severity of the disease has been found. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2013]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.739 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LRR1	NM_152329.4	c.-22G>C		5_prime_UTR_variant	1/4	ENST00000298288.11
LRR1	NM_203467.2	c.-22G>C		5_prime_UTR_variant	1/3
LRR1	NR_037792.2	n.60G>C		non_coding_transcript_exon_variant	1/6
LRR1	NR_037793.2	n.60G>C		non_coding_transcript_exon_variant	1/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRR1	ENST00000298288.11	c.-22G>C		5_prime_UTR_variant	1/4	1	NM_152329.4	P1

Frequencies

GnomAD3 genomes AF: 0.710 AC: 107994 AN: 152138 Hom.: 39467 Cov.: 36

Gnomad AFR AF: 0.733

Gnomad AMI AF: 0.738

Gnomad AMR AF: 0.682

Gnomad ASJ AF: 0.714

Gnomad EAS AF: 0.146

Gnomad SAS AF: 0.531

Gnomad FIN AF: 0.793

Gnomad MID AF: 0.709

Gnomad NFE AF: 0.744

Gnomad OTH AF: 0.700

GnomAD3 exomes AF: 0.651 AC: 143373 AN: 220298 Hom.: 49601 AF XY: 0.648 AC XY: 77238 AN XY: 119134

Gnomad AFR exome AF: 0.725

Gnomad AMR exome AF: 0.606

Gnomad ASJ exome AF: 0.725

Gnomad EAS exome AF: 0.148

Gnomad SAS exome AF: 0.540

Gnomad FIN exome AF: 0.773

Gnomad NFE exome AF: 0.742

Gnomad OTH exome AF: 0.688

GnomAD4 exome AF: 0.713 AC: 1026057 AN: 1439008 Hom.: 375571 Cov.: 46 AF XY: 0.708 AC XY: 505283 AN XY: 713432

Gnomad4 AFR exome AF: 0.724

Gnomad4 AMR exome AF: 0.618

Gnomad4 ASJ exome AF: 0.729

Gnomad4 EAS exome AF: 0.120

Gnomad4 SAS exome AF: 0.543

Gnomad4 FIN exome AF: 0.772

Gnomad4 NFE exome AF: 0.749

Gnomad4 OTH exome AF: 0.684

GnomAD4 genome AF: 0.710 AC: 108089 AN: 152256 Hom.: 39507 Cov.: 36 AF XY: 0.706 AC XY: 52536 AN XY: 74448

Gnomad4 AFR AF: 0.733

Gnomad4 AMR AF: 0.682

Gnomad4 ASJ AF: 0.714

Gnomad4 EAS AF: 0.146

Gnomad4 SAS AF: 0.530

Gnomad4 FIN AF: 0.793

Gnomad4 NFE AF: 0.744

Gnomad4 OTH AF: 0.699

Alfa AF: 0.682 Hom.: 4247

Bravo AF: 0.701

Asia WGS AF: 0.405 AC: 1410 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
Cadd	Benign	0.67
Dann	Benign	0.59
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs2281836; hg19: chr14-50065717; COSMIC: COSV53563336; COSMIC: COSV53563336;