Genetic Variant NM_015155.3:c.1924G>A (chr10-814747-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_015155.3(LARP4B):c.1924G>A(p.Ala642Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000528 in 1,590,218 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00019 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000038 ( 0 hom. )

Consequence

LARP4B
NM_015155.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.12

Publications

5 publications found

Variant links:

Genes affected

LARP4B (HGNC:28987): (La ribonucleoprotein 4B) This gene encodes a member of an evolutionarily conserved protein family implicated in RNA metabolism and translation. Members of this family are characterized by the presence of an La motif, which is often located adjacent to one or more RNA recognition motifs (RRM). Together, the two motifs constitute the functional region of the protein and enable its interaction with the RNA substrate. This protein family is divided into five sub-families: the genuine La proteins and four La-related protein (LARP) sub-families. The protein encoded by this gene belongs to LARP sub-family 4. It is a cytoplasmic protein that may play a stimulatory role in translation. [provided by RefSeq, Oct 2012]

LARP4B links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.04734412).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LARP4B	NM_015155.3 link	c.1924G>A	p.Ala642Thr	missense_variant	Exon 17 of 18	ENST00000316157.8	NP_055970.1	Q92615

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LARP4B	ENST00000316157.8 link	c.1924G>A	p.Ala642Thr	missense_variant	Exon 17 of 18	1	NM_015155.3	ENSP00000326128.3		Q92615

Frequencies

GnomAD3 genomes

AF:

0.000191

AC:

AN:

152216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000675

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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

GnomAD2 exomes

AF:

0.0000558

AC:

AN:

215144

AF XY:

0.0000690

show subpopulations

Gnomad AFR exome

AF:

0.000620

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000425

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000382

AC:

AN:

1438002

Hom.:

Cov.:

AF XY:

0.0000238

AC XY:

AN XY:

713458

show subpopulations

African (AFR)

AF:

0.000487

AC:

AN:

32822

American (AMR)

AF:

0.0000718

AC:

AN:

41810

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25754

East Asian (EAS)

AF:

0.00

AC:

AN:

38118

South Asian (SAS)

AF:

0.00

AC:

AN:

82918

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51536

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5746

European-Non Finnish (NFE)

AF:

0.0000318

AC:

AN:

1099886

Other (OTH)

AF:

0.0000168

AC:

AN:

59412

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.455

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.000191

AC:

AN:

152216

Hom.:

Cov.:

AF XY:

0.000256

AC XY:

AN XY:

74358

show subpopulations

African (AFR)

AF:

0.000675

AC:

AN:

41454

American (AMR)

AF:

0.00

AC:

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5202

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68038

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.516

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.000109

Hom.:

Bravo

AF:

0.000178

ESP6500AA

AF:

0.000908

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000413

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Sep 26, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.1924G>A (p.A642T) alteration is located in exon 16 (coding exon 16) of the LARP4B gene. This alteration results from a G to A substitution at nucleotide position 1924, causing the alanine (A) at amino acid position 642 to be replaced by a threonine (T). 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

0.069

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.50

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.029

T;T;T

Eigen

Benign

-0.098

Eigen_PC

Benign

-0.053

FATHMM_MKL

Uncertain

0.82

LIST_S2

Benign

0.82

T;T;.

M_CAP

Benign

0.024

MetaRNN

Benign

0.047

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.1

.;M;M

PhyloP100

2.1

PrimateAI

Benign

0.37

PROVEAN

Benign

-0.93

.;.;N

REVEL

Benign

0.057

Sift

Benign

0.60

.;.;T

Sift4G

Uncertain

0.010

D;T;T

Polyphen

0.051

.;B;B

Vest4

0.16, 0.16

MVP

0.24

MPC

0.31

ClinPred

0.044

GERP RS

3.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.067

gMVP

0.31

Mutation Taster

=85/15

polymorphism

(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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NM_015155.3:c.1924G>A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over