Variant 14-49598999-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.880

Variant links:

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]

LRR1 links:

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 links:

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ACMG classification

Classification made for transcript

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	Effect	#exon/exons	MANE	Protein
LRR1	NM_152329.4 linkuse as main transcript	c.-22G>C	5_prime_UTR_variant	1/4	ENST00000298288.11	NP_689542.2
LRR1	NM_203467.2 linkuse as main transcript	c.-22G>C	5_prime_UTR_variant	1/3		NP_982292.1
LRR1	NR_037792.2 linkuse as main transcript	n.60G>C	non_coding_transcript_exon_variant	1/6
LRR1	NR_037793.2 linkuse as main transcript	n.60G>C	non_coding_transcript_exon_variant	1/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRR1	ENST00000298288.11 linkuse as main transcript	c.-22G>C		5_prime_UTR_variant	1/4	1	NM_152329.4	ENSP00000298288	P1	Q96L50-1

Frequencies

GnomAD3 genomes

AF:

0.710

AC:

107994

AN:

152138

Hom.:

39467

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.708

AC XY:

505283

AN XY:

713432

show subpopulations

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.:

AF XY:

0.706

AC XY:

52536

AN XY:

74448

show subpopulations

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over