12-50437111-T-C

Position:

• chr12-50437111-T-C

Variant summary

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

The NM_052879.5(LARP4):​c.536-624T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.822 in 152,112 control chromosomes in the GnomAD database, including 54,505 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 0.82 (54505 hom., cov: 31)
• Consequence: LARP4 NM_052879.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.43

Genes affected

LARP4 (HGNC:24320): (La ribonucleoprotein 4) Enables mRNA 3'-UTR binding activity and poly(A) binding activity. Involved in cytoskeleton organization; positive regulation of translation; and regulation of cell morphogenesis. Located in cytosol. Colocalizes with cytoplasmic stress granule; cytosolic small ribosomal subunit; and polysome. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.954 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LARP4	NM_052879.5	c.536-624T>C		intron_variant		ENST00000398473.7	NP_443111.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LARP4	ENST00000398473.7	c.536-624T>C		intron_variant		1	NM_052879.5	ENSP00000381490.2

Frequencies

GnomAD3 genomes AF: 0.822 AC: 124994 AN: 151994 Hom.: 54477 Cov.: 31

Gnomad AFR AF: 0.500

Gnomad AMI AF: 0.953

Gnomad AMR AF: 0.893

Gnomad ASJ AF: 0.905

Gnomad EAS AF: 0.977

Gnomad SAS AF: 0.881

Gnomad FIN AF: 0.983

Gnomad MID AF: 0.899

Gnomad NFE AF: 0.954

Gnomad OTH AF: 0.844

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

GnomAD4 genome AF: 0.822 AC: 125062 AN: 152112 Hom.: 54505 Cov.: 31 AF XY: 0.828 AC XY: 61559 AN XY: 74352

Gnomad4 AFR AF: 0.500

Gnomad4 AMR AF: 0.893

Gnomad4 ASJ AF: 0.905

Gnomad4 EAS AF: 0.976

Gnomad4 SAS AF: 0.883

Gnomad4 FIN AF: 0.983

Gnomad4 NFE AF: 0.954

Gnomad4 OTH AF: 0.846

Alfa AF: 0.832 Hom.: 4248

Bravo AF: 0.802

Asia WGS AF: 0.890 AC: 3095 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.42
DANN	Benign	0.42

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: rs4424740; hg19: chr12-50830894;