rs4131364

Variant names:

• chr11-812188-G-A
• rs4131364
• NM_001004.4:c.173-347G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001004.4(RPLP2):​c.173-347G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.428 in 402,276 control chromosomes in the GnomAD database, including 40,852 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 0.41 (14319 hom., cov: 33)
  • Exomes 𝑓: 0.44 (26533 hom.)
• Consequence: RPLP2 NM_001004.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.278
• Publications: 24 publications found

Genes affected

RPLP2 (HGNC:10377): (ribosomal protein lateral stalk subunit P2) 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 phosphoprotein that is a component of the 60S subunit. The protein, which is a functional equivalent of the E. coli L7/L12 ribosomal protein, belongs to the L12P family of ribosomal proteins. It plays an important role in the elongation step of protein synthesis. Unlike most ribosomal proteins, which are basic, the encoded protein is acidic. Its C-terminal end is nearly identical to the C-terminal ends of the ribosomal phosphoproteins P0 and P1. The P2 protein can interact with P0 and P1 to form a pentameric complex consisting of P1 and P2 dimers, and a P0 monomer. The protein 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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.534 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPLP2	NM_001004.4	c.173-347G>A		intron_variant	Intron 3 of 4	ENST00000321153.9	NP_000995.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPLP2	ENST00000321153.9	c.173-347G>A		intron_variant	Intron 3 of 4	1	NM_001004.4	ENSP00000322419.4

Frequencies

GnomAD3 genomes AF: 0.407 AC: 61924 AN: 151970 Hom.: 14306 Cov.: 33

Gnomad AFR AF: 0.195

Gnomad AMI AF: 0.606

Gnomad AMR AF: 0.543

Gnomad ASJ AF: 0.375

Gnomad EAS AF: 0.257

Gnomad SAS AF: 0.220

Gnomad FIN AF: 0.576

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.504

Gnomad OTH AF: 0.419

GnomAD4 exome AF: 0.440 AC: 110029 AN: 250188 Hom.: 26533 Cov.: 0 AF XY: 0.417 AC XY: 55557 AN XY: 133210

African (AFR) AF: 0.197 AC: 1485 AN: 7520

American (AMR) AF: 0.595 AC: 7012 AN: 11792

Ashkenazi Jewish (ASJ) AF: 0.369 AC: 2584 AN: 6998

East Asian (EAS) AF: 0.263 AC: 3382 AN: 12846

South Asian (SAS) AF: 0.227 AC: 8998 AN: 39698

European-Finnish (FIN) AF: 0.579 AC: 7258 AN: 12530

Middle Eastern (MID) AF: 0.414 AC: 414 AN: 1000

European-Non Finnish (NFE) AF: 0.505 AC: 72899 AN: 144304

Other (OTH) AF: 0.444 AC: 5997 AN: 13500

GnomAD4 genome AF: 0.407 AC: 61959 AN: 152088 Hom.: 14319 Cov.: 33 AF XY: 0.408 AC XY: 30326 AN XY: 74340

African (AFR) AF: 0.195 AC: 8076 AN: 41504

American (AMR) AF: 0.543 AC: 8295 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.375 AC: 1300 AN: 3468

East Asian (EAS) AF: 0.257 AC: 1328 AN: 5176

South Asian (SAS) AF: 0.222 AC: 1070 AN: 4816

European-Finnish (FIN) AF: 0.576 AC: 6086 AN: 10574

Middle Eastern (MID) AF: 0.446 AC: 131 AN: 294

European-Non Finnish (NFE) AF: 0.504 AC: 34235 AN: 67970

Other (OTH) AF: 0.419 AC: 885 AN: 2110

Alfa AF: 0.464 Hom.: 15691

Bravo AF: 0.400

Asia WGS AF: 0.247 AC: 864 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	1.6
DANN	Benign	0.53
PhyloP100		-0.28
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: rs4131364; hg19: chr11-812188;