Variant 4-128091463-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_018078.4(LARP1B):c.619G>A(p.Val207Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000211 in 1,610,160 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

LARP1B
NM_018078.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.78

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.037913293).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LARP1B	NM_018078.4 linkuse as main transcript	c.619G>A	p.Val207Met	missense_variant	7/20	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.619G>A	p.Val207Met	missense_variant	7/20	5	NM_018078.4	ENSP00000321997.6		Q659C4-1

Frequencies

GnomAD3 genomes

AF:

0.000105

AC:

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000338

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000361

AC:

AN:

249268

Hom.:

AF XY:

0.0000372

AC XY:

AN XY:

134560

show subpopulations

Gnomad AFR exome

AF:

0.000554

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000123

AC:

AN:

1457860

Hom.:

Cov.:

AF XY:

0.00000965

AC XY:

AN XY:

725230

show subpopulations

Gnomad4 AFR exome

AF:

0.000509

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.000105

AC:

AN:

152300

Hom.:

Cov.:

AF XY:

0.000134

AC XY:

AN XY:

74476

show subpopulations

Gnomad4 AFR

AF:

0.000337

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000197

Hom.:

Bravo

AF:

0.000151

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000494

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

Dec 09, 2024

The c.619G>A (p.V207M) alteration is located in exon 7 (coding exon 5) of the LARP1B gene. This alteration results from a G to A substitution at nucleotide position 619, causing the valine (V) at amino acid position 207 to be replaced by a methionine (M). 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

0.14

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Benign

0.84

DEOGEN2

Benign

0.0024

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

Eigen

Benign

-0.48

Eigen_PC

Benign

-0.31

FATHMM_MKL

Benign

0.74

LIST_S2

Uncertain

0.94

D;D;D;D;D;D;D;D

M_CAP

Benign

0.0018

MetaRNN

Benign

0.038

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

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.10

N;.;.;N;.;.;.;.

PrimateAI

Uncertain

0.51

PROVEAN

Benign

0.090

N;N;N;N;N;.;.;.

REVEL

Benign

0.037

Sift

Benign

0.43

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

Sift4G

Benign

0.50

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

Polyphen

0.0020

B;.;.;B;B;.;.;.

Vest4

0.028

MVP

0.30

MPC

0.16

ClinPred

0.045

GERP RS

2.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.026

gMVP

0.33

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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