rs10904575

chr10-844312-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015155.3(LARP4B):c.509+665C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.38 in 152,076 control chromosomes in the GnomAD database, including 11,496 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 0.38 (11496 hom., cov: 33)
• Consequence: LARP4B NM_015155.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.728

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.586 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LARP4B	NM_015155.3	c.509+665C>T		intron_variant		ENST00000316157.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LARP4B	ENST00000316157.8	c.509+665C>T		intron_variant		1	NM_015155.3	P1
LARP4B	ENST00000688365.1	c.362+665C>T		intron_variant
LARP4B	ENST00000689323.1	c.3500+665C>T		intron_variant
LARP4B	ENST00000690516.1	c.431-1244C>T		intron_variant, NMD_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.380 AC: 57726 AN: 151958 Hom.: 11483 Cov.: 33

Gnomad AFR AF: 0.297

Gnomad AMI AF: 0.474

Gnomad AMR AF: 0.291

Gnomad ASJ AF: 0.411

Gnomad EAS AF: 0.393

Gnomad SAS AF: 0.604

Gnomad FIN AF: 0.529

Gnomad MID AF: 0.396

Gnomad NFE AF: 0.408

Gnomad OTH AF: 0.364

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.380 AC: 57760 AN: 152076 Hom.: 11496 Cov.: 33 AF XY: 0.387 AC XY: 28729 AN XY: 74312

Gnomad4 AFR AF: 0.296

Gnomad4 AMR AF: 0.291

Gnomad4 ASJ AF: 0.411

Gnomad4 EAS AF: 0.394

Gnomad4 SAS AF: 0.604

Gnomad4 FIN AF: 0.529

Gnomad4 NFE AF: 0.408

Gnomad4 OTH AF: 0.370

Alfa AF: 0.391 Hom.: 4634

Bravo AF: 0.351

Asia WGS AF: 0.499 AC: 1736 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	1.2
Dann	Benign	0.41

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: rs10904575; hg19: chr10-890252;