rs2281836

Variant names:

• chr14-49598999-G-C
• rs2281836
• NM_152329.4:c.-22G>C

Your query was ambiguous. Multiple possible variants found:

• chr14-49598999-G-C
• chr14-49598999-G-T

Variant summary

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

The NM_152329.4(LRR1):​c.-22G>C variant causes a 5 prime UTR premature start codon gain 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_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.880
• Publications: 29 publications found

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]

RPS29 Gene-Disease associations (from GenCC):

• Diamond-Blackfan anemia 13

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae)
• Diamond-Blackfan anemia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
LRR1	NM_152329.4	c.-22G>C		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 4	ENST00000298288.11	NP_689542.2
LRR1	NM_152329.4	c.-22G>C		5_prime_UTR_variant	Exon 1 of 4	ENST00000298288.11	NP_689542.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRR1	ENST00000298288.11	c.-22G>C		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 4	1	NM_152329.4	ENSP00000298288.6
LRR1	ENST00000298288.11	c.-22G>C		5_prime_UTR_variant	Exon 1 of 4	1	NM_152329.4	ENSP00000298288.6

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

GnomAD2 exomes AF: 0.651 AC: 143373 AN: 220298 AF XY: 0.648

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 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

African (AFR) AF: 0.724 AC: 23972 AN: 33088

American (AMR) AF: 0.618 AC: 25350 AN: 41028

Ashkenazi Jewish (ASJ) AF: 0.729 AC: 18514 AN: 25410

East Asian (EAS) AF: 0.120 AC: 4711 AN: 39174

South Asian (SAS) AF: 0.543 AC: 45361 AN: 83564

European-Finnish (FIN) AF: 0.772 AC: 40013 AN: 51806

Middle Eastern (MID) AF: 0.664 AC: 3794 AN: 5712

European-Non Finnish (NFE) AF: 0.749 AC: 823746 AN: 1099870

Other (OTH) AF: 0.684 AC: 40596 AN: 59356

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

African (AFR) AF: 0.733 AC: 30473 AN: 41546

American (AMR) AF: 0.682 AC: 10440 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.714 AC: 2480 AN: 3472

East Asian (EAS) AF: 0.146 AC: 756 AN: 5184

South Asian (SAS) AF: 0.530 AC: 2556 AN: 4824

European-Finnish (FIN) AF: 0.793 AC: 8411 AN: 10600

Middle Eastern (MID) AF: 0.721 AC: 212 AN: 294

European-Non Finnish (NFE) AF: 0.744 AC: 50610 AN: 68002

Other (OTH) AF: 0.699 AC: 1478 AN: 2114

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
PhyloP100		-0.88
PromoterAI		-0.13	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=300/0	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: rs2281836; hg19: chr14-50065717; COSMIC: COSV53563336; COSMIC: COSV53563336;