rs917570

chr11-67429073-C-Gchr11-67429073-C-T

Variant summary

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

The NM_003952.3(RPS6KB2):c.120-47C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.37 in 1,612,102 control chromosomes in the GnomAD database, including 116,566 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 0.30 (7804 hom., cov: 31)
  • Exomes 𝑓: 0.38 (108762 hom.)
• Consequence: RPS6KB2 NM_003952.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.456

Genes affected

RPS6KB2 (HGNC:10437): (ribosomal protein S6 kinase B2) This gene encodes a member of the RSK (ribosomal S6 kinase) family of serine/threonine kinases. This kinase contains a kinase catalytic domain and phosphorylates the S6 ribosomal protein and eukaryotic translation initiation factor 4B (eIF4B). Phosphorylation of S6 leads to an increase in protein synthesis and cell proliferation. [provided by RefSeq, Jan 2015]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.403 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RPS6KB2	NM_003952.3	c.120-47C>G		intron_variant		ENST00000312629.10
RPS6KB2	XM_047427395.1	c.120-47C>G		intron_variant
RPS6KB2	XM_047427396.1	c.120-47C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RPS6KB2	ENST00000312629.10	c.120-47C>G		intron_variant		1	NM_003952.3	P1

Frequencies

GnomAD3 genomes AF: 0.305 AC: 46251 AN: 151644 Hom.: 7808 Cov.: 31

Gnomad AFR AF: 0.196

Gnomad AMI AF: 0.365

Gnomad AMR AF: 0.237

Gnomad ASJ AF: 0.277

Gnomad EAS AF: 0.140

Gnomad SAS AF: 0.217

Gnomad FIN AF: 0.302

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.407

Gnomad OTH AF: 0.305

GnomAD3 exomes AF: 0.303 AC: 75497 AN: 248882 Hom.: 12861 AF XY: 0.310 AC XY: 41849 AN XY: 135156

Gnomad AFR exome AF: 0.198

Gnomad AMR exome AF: 0.188

Gnomad ASJ exome AF: 0.278

Gnomad EAS exome AF: 0.137

Gnomad SAS exome AF: 0.225

Gnomad FIN exome AF: 0.305

Gnomad NFE exome AF: 0.401

Gnomad OTH exome AF: 0.332

GnomAD4 exome AF: 0.376 AC: 549655 AN: 1460340 Hom.: 108762 Cov.: 38 AF XY: 0.372 AC XY: 270605 AN XY: 726460

Gnomad4 AFR exome AF: 0.192

Gnomad4 AMR exome AF: 0.191

Gnomad4 ASJ exome AF: 0.275

Gnomad4 EAS exome AF: 0.139

Gnomad4 SAS exome AF: 0.232

Gnomad4 FIN exome AF: 0.312

Gnomad4 NFE exome AF: 0.416

Gnomad4 OTH exome AF: 0.349

GnomAD4 genome AF: 0.305 AC: 46247 AN: 151762 Hom.: 7804 Cov.: 31 AF XY: 0.294 AC XY: 21796 AN XY: 74150

Gnomad4 AFR AF: 0.196

Gnomad4 AMR AF: 0.237

Gnomad4 ASJ AF: 0.277

Gnomad4 EAS AF: 0.139

Gnomad4 SAS AF: 0.217

Gnomad4 FIN AF: 0.302

Gnomad4 NFE AF: 0.407

Gnomad4 OTH AF: 0.301

Alfa AF: 0.263 Hom.: 1020

Bravo AF: 0.303

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	3.5
Dann	Benign	0.59
RBP_binding_hub_radar		1.0
RBP_regulation_power_radar		2.3

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: rs917570; hg19: chr11-67196544; COSMIC: COSV57049122; COSMIC: COSV57049122;