4-128077958-G-C

Position:

• chr4-128077958-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_018078.4(LARP1B):​c.213G>C​(p.Lys71Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000707 in 1,413,668 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: LARP1B NM_018078.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.11

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.25721642).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LARP1B	NM_018078.4	c.213G>C	p.Lys71Asn	missense_variant	4/20	ENST00000326639.11	NP_060548.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LARP1B	ENST00000326639.11	c.213G>C	p.Lys71Asn	missense_variant	4/20	5	NM_018078.4	ENSP00000321997	A2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.07e-7 AC: 1 AN: 1413668 Hom.: 0 Cov.: 29 AF XY: 0.00000143 AC XY: 1 AN XY: 701684

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000257

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 14, 2023

The c.213G>C (p.K71N) alteration is located in exon 4 (coding exon 2) of the LARP1B gene. This alteration results from a G to C substitution at nucleotide position 213, causing the lysine (K) at amino acid position 71 to be replaced by an asparagine (N). 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	Pathogenic	0.64
BayesDel_addAF	Benign	-0.077	T
BayesDel_noAF	Benign	-0.35
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.15	T;.;.;.;T;.;.;.
Eigen	Benign	0.020
Eigen_PC	Benign	-0.058
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Uncertain	0.88	D;D;T;D;D;D;D;D
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.26	T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.81	T
MutationAssessor	Uncertain	2.6	M;.;.;M;.;.;.;.
MutationTaster	Benign	0.93	D;D;D;D;D;N;N;N
PrimateAI	Uncertain	0.58	T
PROVEAN	Uncertain	-3.0	D;D;N;D;D;.;.;.
REVEL	Benign	0.086
Sift	Uncertain	0.0030	D;D;T;D;D;.;.;.
Sift4G	Uncertain	0.0030	D;D;T;D;D;.;.;.
Polyphen		0.99	D;.;.;P;D;.;.;.
Vest4		0.36
MutPred		0.25		Loss of methylation at K71 (P = 0.007);Loss of methylation at K71 (P = 0.007);Loss of methylation at K71 (P = 0.007);Loss of methylation at K71 (P = 0.007);Loss of methylation at K71 (P = 0.007);.;.;.;
MVP		0.69
MPC		0.25
ClinPred		0.96	D
GERP RS		1.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.29
gMVP		0.28

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

Other links and lift over

dbSNP: rs1768651528; hg19: chr4-128999113;