14-49598999-G-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.880

Publications

29 publications found

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 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

RPS29 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152329.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
LRR1	NM_152329.4	MANE Select	c.-22G>C	5_prime_UTR_premature_start_codon_gain	Exon 1 of 4	NP_689542.2
LRR1	NM_152329.4	MANE Select	c.-22G>C	5_prime_UTR	Exon 1 of 4	NP_689542.2
LRR1	NM_203467.2		c.-22G>C	5_prime_UTR_premature_start_codon_gain	Exon 1 of 3	NP_982292.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
LRR1	ENST00000298288.11	TSL:1 MANE Select	c.-22G>C	5_prime_UTR_premature_start_codon_gain	Exon 1 of 4	ENSP00000298288.6
LRR1	ENST00000318317.8	TSL:1	c.-22G>C	5_prime_UTR_premature_start_codon_gain	Exon 1 of 3	ENSP00000315628.4
LRR1	ENST00000540712.1	TSL:1	n.-22G>C	5_prime_UTR_premature_start_codon_gain	Exon 1 of 5	ENSP00000439452.1

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

GnomAD2 exomes

AF:

0.651

AC:

143373

AN:

220298

AF XY:

0.648

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 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

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

15126

30252

45377

60503

75629

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

19938

39876

59814

79752

99690

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.710

AC:

108089

AN:

152256

Hom.:

39507

Cov.:

AF XY:

0.706

AC XY:

52536

AN XY:

74448

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1607

3213

4820

6426

8033

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

810

1620

2430

3240

4050

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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 v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

0.67

(source)

DANN

Benign

0.59

PhyloP100

-0.88

PromoterAI

-0.13

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=300/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over