15-66503642-A-G

Position:

• chr15-66503642-A-G

Variant summary

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

The NM_000968.4(RPL4):​c.4-113T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.861 in 1,171,732 control chromosomes in the GnomAD database, including 434,812 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 0.89 (60642 hom., cov: 33)
  • Exomes 𝑓: 0.86 (374170 hom.)
• Consequence: RPL4 NM_000968.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.213

Genes affected

RPL4 (HGNC:10353): (ribosomal protein L4) Ribosomes, the organelles that catalyze protein synthesis, consist of a small 40S subunit and a large 60S subunit. Together these subunits are composed of 4 RNA species and approximately 80 structurally distinct proteins. This gene encodes a ribosomal protein that is a component of the 60S subunit. The protein belongs to the L4E family of ribosomal proteins. It is located in the cytoplasm. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.963 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RPL4	NM_000968.4	c.4-113T>C		intron_variant		ENST00000307961.11	NP_000959.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPL4	ENST00000307961.11	c.4-113T>C		intron_variant		1	NM_000968.4	ENSP00000311430	P1

Frequencies

GnomAD3 genomes AF: 0.891 AC: 135540 AN: 152156 Hom.: 60597 Cov.: 33

Gnomad AFR AF: 0.971

Gnomad AMI AF: 0.866

Gnomad AMR AF: 0.875

Gnomad ASJ AF: 0.873

Gnomad EAS AF: 0.931

Gnomad SAS AF: 0.922

Gnomad FIN AF: 0.851

Gnomad MID AF: 0.924

Gnomad NFE AF: 0.848

Gnomad OTH AF: 0.884

GnomAD4 exome AF: 0.856 AC: 872710 AN: 1019458 Hom.: 374170 AF XY: 0.857 AC XY: 428506 AN XY: 499742

Gnomad4 AFR exome AF: 0.977

Gnomad4 AMR exome AF: 0.864

Gnomad4 ASJ exome AF: 0.875

Gnomad4 EAS exome AF: 0.912

Gnomad4 SAS exome AF: 0.924

Gnomad4 FIN exome AF: 0.843

Gnomad4 NFE exome AF: 0.845

Gnomad4 OTH exome AF: 0.874

GnomAD4 genome AF: 0.891 AC: 135641 AN: 152274 Hom.: 60642 Cov.: 33 AF XY: 0.893 AC XY: 66452 AN XY: 74436

Gnomad4 AFR AF: 0.971

Gnomad4 AMR AF: 0.875

Gnomad4 ASJ AF: 0.873

Gnomad4 EAS AF: 0.930

Gnomad4 SAS AF: 0.922

Gnomad4 FIN AF: 0.851

Gnomad4 NFE AF: 0.848

Gnomad4 OTH AF: 0.885

Alfa AF: 0.851 Hom.: 12741

Bravo AF: 0.894

Asia WGS AF: 0.927 AC: 3223 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.8
DANN	Benign	0.37

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: rs8043062; hg19: chr15-66795980;