rs10752021

Positions:

• chr10-828956-C-A
• chr10-828956-C-G

Variant summary

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

The NM_015155.3(LARP4B):​c.1125+429G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.561 in 152,072 control chromosomes in the GnomAD database, including 24,367 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 0.56 (24367 hom., cov: 33)
• Consequence: LARP4B NM_015155.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.449

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=-0.98).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.66 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LARP4B	NM_015155.3	c.1125+429G>T		intron_variant		ENST00000316157.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LARP4B	ENST00000316157.8	c.1125+429G>T		intron_variant		1	NM_015155.3	P1
LARP4B	ENST00000688365.1	c.978+429G>T		intron_variant
LARP4B	ENST00000689323.1	c.4116+429G>T		intron_variant
LARP4B	ENST00000690516.1	c.*497+429G>T		intron_variant, NMD_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.561 AC: 85233 AN: 151952 Hom.: 24335 Cov.: 33

Gnomad AFR AF: 0.527

Gnomad AMI AF: 0.557

Gnomad AMR AF: 0.473

Gnomad ASJ AF: 0.476

Gnomad EAS AF: 0.369

Gnomad SAS AF: 0.679

Gnomad FIN AF: 0.690

Gnomad MID AF: 0.456

Gnomad NFE AF: 0.593

Gnomad OTH AF: 0.542

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

GnomAD4 genome AF: 0.561 AC: 85325 AN: 152072 Hom.: 24367 Cov.: 33 AF XY: 0.563 AC XY: 41858 AN XY: 74316

Gnomad4 AFR AF: 0.528

Gnomad4 AMR AF: 0.473

Gnomad4 ASJ AF: 0.476

Gnomad4 EAS AF: 0.370

Gnomad4 SAS AF: 0.679

Gnomad4 FIN AF: 0.690

Gnomad4 NFE AF: 0.593

Gnomad4 OTH AF: 0.546

Alfa AF: 0.570 Hom.: 7750

Bravo AF: 0.536

Asia WGS AF: 0.551 AC: 1917 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.6
DANN	Benign	0.52

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: rs10752021; hg19: chr10-874896;