rs180519

Positions:

• chr17-59938910-G-A

Variant summary

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

The NM_003161.4(RPS6KB1):​c.1120-1926G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.559 in 151,994 control chromosomes in the GnomAD database, including 25,843 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 (25843 hom., cov: 31)
• Consequence: RPS6KB1 NM_003161.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.801

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.811 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RPS6KB1	NM_003161.4	c.1120-1926G>A		intron_variant		ENST00000225577.9	NP_003152.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPS6KB1	ENST00000225577.9	c.1120-1926G>A		intron_variant		1	NM_003161.4	ENSP00000225577	A1

Frequencies

GnomAD3 genomes AF: 0.559 AC: 84868 AN: 151876 Hom.: 25791 Cov.: 31

Gnomad AFR AF: 0.818

Gnomad AMI AF: 0.498

Gnomad AMR AF: 0.530

Gnomad ASJ AF: 0.417

Gnomad EAS AF: 0.562

Gnomad SAS AF: 0.428

Gnomad FIN AF: 0.429

Gnomad MID AF: 0.551

Gnomad NFE AF: 0.445

Gnomad OTH AF: 0.554

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

GnomAD4 genome AF: 0.559 AC: 84980 AN: 151994 Hom.: 25843 Cov.: 31 AF XY: 0.556 AC XY: 41270 AN XY: 74282

Gnomad4 AFR AF: 0.818

Gnomad4 AMR AF: 0.530

Gnomad4 ASJ AF: 0.417

Gnomad4 EAS AF: 0.561

Gnomad4 SAS AF: 0.425

Gnomad4 FIN AF: 0.429

Gnomad4 NFE AF: 0.445

Gnomad4 OTH AF: 0.559

Alfa AF: 0.469 Hom.: 16915

Bravo AF: 0.576

Asia WGS AF: 0.567 AC: 1973 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.81
DANN	Benign	0.38
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		0.98

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: rs180519; hg19: chr17-58016271;