Variant chr4-128077954-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_018078.4(LARP1B):c.209G>A(p.Arg70His) variant causes a missense change. The variant allele was found at a frequency of 0.00000635 in 1,416,522 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)

Exomes 𝑓: 0.0000064 ( 0 hom. )

Consequence

LARP1B
NM_018078.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.68

Variant links:

Genes affected

LARP1B (HGNC:24704): (La ribonucleoprotein 1B) This gene encodes a protein containing domains found in the La related protein of Drosophila melanogaster. La motif-containing proteins are thought to be RNA-binding proteins, where the La motif and adjacent amino acids fold into an RNA recognition motif. The La motif is also found in proteins unrelated to the La protein. Alternative splicing has been observed at this locus and multiple variants, encoding distinct isoforms, are described. Additional splice variation has been identified but the full-length nature of these transcripts has not been determined. [provided by RefSeq, Jun 2013]

LARP1B links:

LARP1B (HGNC:):

LARP1B links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.29263902).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LARP1B	NM_018078.4 linkuse as main transcript	c.209G>A	p.Arg70His	missense_variant	4/20	ENST00000326639.11	NP_060548.2	Q659C4-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LARP1B	ENST00000326639.11 linkuse as main transcript	c.209G>A	p.Arg70His	missense_variant	4/20	5	NM_018078.4	ENSP00000321997.6		Q659C4-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000227

AC:

AN:

220134

Hom.:

AF XY:

0.0000168

AC XY:

AN XY:

119368

show subpopulations

Gnomad AFR exome

AF:

0.0000651

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000123

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000189

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000635

AC:

AN:

1416522

Hom.:

Cov.:

AF XY:

0.00000427

AC XY:

AN XY:

703278

show subpopulations

Gnomad4 AFR exome

AF:

0.0000637

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000102

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000274

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000302

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 20, 2024

The c.209G>A (p.R70H) alteration is located in exon 4 (coding exon 2) of the LARP1B gene. This alteration results from a G to A substitution at nucleotide position 209, causing the arginine (R) at amino acid position 70 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.27

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.045

T;.;.;.;T;.;.;.

Eigen

Uncertain

0.39

Eigen_PC

Uncertain

0.29

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.95

D;D;T;D;D;D;D;D

M_CAP

Benign

0.027

MetaRNN

Benign

0.29

T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.64

MutationAssessor

Uncertain

2.4

M;.;.;M;.;.;.;.

PrimateAI

Uncertain

0.64

PROVEAN

Uncertain

-2.8

D;D;D;D;D;.;.;.

REVEL

Benign

0.15

Sift

Uncertain

0.0040

D;D;D;D;D;.;.;.

Sift4G

Uncertain

0.0080

D;D;D;D;D;.;.;.

Polyphen

1.0

D;.;.;D;D;.;.;.

Vest4

0.34

MutPred

0.20

Gain of glycosylation at S67 (P = 0.0122);Gain of glycosylation at S67 (P = 0.0122);Gain of glycosylation at S67 (P = 0.0122);Gain of glycosylation at S67 (P = 0.0122);Gain of glycosylation at S67 (P = 0.0122);.;.;.;

MVP

0.74

MPC

0.71

ClinPred

0.72

GERP RS

3.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.10

gMVP

0.19

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over