rs10904575

Variant names:

• chr10-844312-G-A
• rs10904575
• NM_015155.3:c.509+665C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 0 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015155.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LARP4B	NM_015155.3	MANE Select	c.509+665C>T		intron	N/A	NP_055970.1
	LARP4B	NM_001351277.2		c.509+665C>T		intron	N/A	NP_001338206.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LARP4B	ENST00000316157.8	TSL:1 MANE Select	c.509+665C>T		intron	N/A	ENSP00000326128.3
	LARP4B	ENST00000689323.1		c.3500+665C>T		intron	N/A	ENSP00000510165.1
	LARP4B	ENST00000688365.1		c.362+665C>T		intron	N/A	ENSP00000509705.1

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

African (AFR) AF: 0.296 AC: 12301 AN: 41492

American (AMR) AF: 0.291 AC: 4439 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.411 AC: 1426 AN: 3470

East Asian (EAS) AF: 0.394 AC: 2034 AN: 5166

South Asian (SAS) AF: 0.604 AC: 2909 AN: 4814

European-Finnish (FIN) AF: 0.529 AC: 5598 AN: 10578

Middle Eastern (MID) AF: 0.401 AC: 118 AN: 294

European-Non Finnish (NFE) AF: 0.408 AC: 27722 AN: 67964

Other (OTH) AF: 0.370 AC: 781 AN: 2108

Alfa AF: 0.388 Hom.: 7187

Bravo AF: 0.351

Asia WGS AF: 0.499 AC: 1736 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.2
DANN	Benign	0.41
PhyloP100		-0.73
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10904575; hg19: chr10-890252;