rs180515

Positions:

• chr17-59946914-A-G

Variant summary

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

The NM_003161.4(RPS6KB1):​c.*126A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.353 in 1,509,254 control chromosomes in the GnomAD database, including 95,242 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 0.33 (8588 hom., cov: 31)
  • Exomes 𝑓: 0.36 (86654 hom.)
• Consequence: RPS6KB1 NM_003161.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.97

Genes affected

RPS6KB1 (HGNC:10436): (ribosomal protein S6 kinase B1) This gene encodes a member of the ribosomal S6 kinase family of serine/threonine kinases. The encoded protein responds to mTOR (mammalian target of rapamycin) signaling to promote protein synthesis, cell growth, and cell proliferation. Activity of this gene has been associated with human cancer. Alternatively spliced transcript variants have been observed. The use of alternative translation start sites results in isoforms with longer or shorter N-termini which may differ in their subcellular localizations. There are two pseudogenes for this gene on chromosome 17. [provided by RefSeq, Jan 2013]

ENSG00000267318 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.428 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RPS6KB1	NM_003161.4	c.*126A>G		3_prime_UTR_variant	15/15	ENST00000225577.9	NP_003152.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPS6KB1	ENST00000225577.9	c.*126A>G		3_prime_UTR_variant	15/15	1	NM_003161.4	ENSP00000225577.4
ENSG00000267318	ENST00000591035.1	c.149+1396A>G		intron_variant		3		ENSP00000468280.1

Frequencies

GnomAD3 genomes AF: 0.332 AC: 50451 AN: 151830 Hom.: 8576 Cov.: 31

Gnomad AFR AF: 0.278

Gnomad AMI AF: 0.430

Gnomad AMR AF: 0.329

Gnomad ASJ AF: 0.303

Gnomad EAS AF: 0.443

Gnomad SAS AF: 0.372

Gnomad FIN AF: 0.332

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.355

Gnomad OTH AF: 0.341

GnomAD4 exome AF: 0.355 AC: 482096 AN: 1357306 Hom.: 86654 Cov.: 31 AF XY: 0.356 AC XY: 236837 AN XY: 665100

Gnomad4 AFR exome AF: 0.277

Gnomad4 AMR exome AF: 0.305

Gnomad4 ASJ exome AF: 0.308

Gnomad4 EAS exome AF: 0.459

Gnomad4 SAS exome AF: 0.384

Gnomad4 FIN exome AF: 0.333

Gnomad4 NFE exome AF: 0.356

Gnomad4 OTH exome AF: 0.345

GnomAD4 genome AF: 0.332 AC: 50499 AN: 151948 Hom.: 8588 Cov.: 31 AF XY: 0.332 AC XY: 24677 AN XY: 74256

Gnomad4 AFR AF: 0.278

Gnomad4 AMR AF: 0.329

Gnomad4 ASJ AF: 0.303

Gnomad4 EAS AF: 0.443

Gnomad4 SAS AF: 0.370

Gnomad4 FIN AF: 0.332

Gnomad4 NFE AF: 0.355

Gnomad4 OTH AF: 0.348

Alfa AF: 0.348 Hom.: 20399

Bravo AF: 0.327

Asia WGS AF: 0.441 AC: 1535 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	9.5
DANN	Benign	0.64

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: rs180515; hg19: chr17-58024275;