rs1292034

chr17-59912499-G-Achr17-59912499-G-Cchr17-59912499-G-T

Variant summary

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

The NM_003161.4(RPS6KB1):c.192-185G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.495 in 508,614 control chromosomes in the GnomAD database, including 66,203 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 (25953 hom., cov: 32)
  • Exomes 𝑓: 0.47 (40250 hom.)
• Consequence: RPS6KB1 NM_003161.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.24

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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.814 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RPS6KB1	NM_003161.4	c.192-185G>A		intron_variant		ENST00000225577.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RPS6KB1	ENST00000225577.9	c.192-185G>A		intron_variant		1	NM_003161.4	A1

Frequencies

GnomAD3 genomes AF: 0.560 AC: 84998 AN: 151856 Hom.: 25897 Cov.: 32

Gnomad AFR AF: 0.821

Gnomad AMI AF: 0.497

Gnomad AMR AF: 0.530

Gnomad ASJ AF: 0.417

Gnomad EAS AF: 0.560

Gnomad SAS AF: 0.427

Gnomad FIN AF: 0.428

Gnomad MID AF: 0.554

Gnomad NFE AF: 0.446

Gnomad OTH AF: 0.557

GnomAD4 exome AF: 0.467 AC: 166495 AN: 356640 Hom.: 40250 AF XY: 0.463 AC XY: 86244 AN XY: 186290

Gnomad4 AFR exome AF: 0.821

Gnomad4 AMR exome AF: 0.468

Gnomad4 ASJ exome AF: 0.421

Gnomad4 EAS exome AF: 0.580

Gnomad4 SAS exome AF: 0.425

Gnomad4 FIN exome AF: 0.429

Gnomad4 NFE exome AF: 0.446

Gnomad4 OTH exome AF: 0.484

GnomAD4 genome AF: 0.560 AC: 85115 AN: 151974 Hom.: 25953 Cov.: 32 AF XY: 0.557 AC XY: 41341 AN XY: 74266

Gnomad4 AFR AF: 0.821

Gnomad4 AMR AF: 0.530

Gnomad4 ASJ AF: 0.417

Gnomad4 EAS AF: 0.559

Gnomad4 SAS AF: 0.424

Gnomad4 FIN AF: 0.428

Gnomad4 NFE AF: 0.446

Gnomad4 OTH AF: 0.562

Alfa AF: 0.468 Hom.: 23200

Bravo AF: 0.577

Asia WGS AF: 0.568 AC: 1975 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
Cadd	Benign	5.9
Dann	Benign	0.27

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: rs1292034; hg19: chr17-57989860;