rs1476792

Positions:

• chr11-67428766-T-C

Variant summary

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

The NM_003952.3(RPS6KB2):​c.78+143T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.437 in 930,166 control chromosomes in the GnomAD database, including 95,614 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 0.52 (23252 hom., cov: 32)
  • Exomes 𝑓: 0.42 (72362 hom.)
• Consequence: RPS6KB2 NM_003952.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.275

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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.798 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RPS6KB2	NM_003952.3	c.78+143T>C		intron_variant		ENST00000312629.10	NP_003943.2
RPS6KB2	XM_047427395.1	c.78+143T>C		intron_variant			XP_047283351.1
RPS6KB2	XM_047427396.1	c.78+143T>C		intron_variant			XP_047283352.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPS6KB2	ENST00000312629.10	c.78+143T>C		intron_variant		1	NM_003952.3	ENSP00000308413	P1

Frequencies

GnomAD3 genomes AF: 0.522 AC: 79379 AN: 151986 Hom.: 23220 Cov.: 32

Gnomad AFR AF: 0.806

Gnomad AMI AF: 0.365

Gnomad AMR AF: 0.509

Gnomad ASJ AF: 0.323

Gnomad EAS AF: 0.293

Gnomad SAS AF: 0.249

Gnomad FIN AF: 0.372

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.428

Gnomad OTH AF: 0.471

GnomAD4 exome AF: 0.420 AC: 326684 AN: 778062 Hom.: 72362 Cov.: 10 AF XY: 0.410 AC XY: 164296 AN XY: 400840

Gnomad4 AFR exome AF: 0.808

Gnomad4 AMR exome AF: 0.575

Gnomad4 ASJ exome AF: 0.319

Gnomad4 EAS exome AF: 0.309

Gnomad4 SAS exome AF: 0.267

Gnomad4 FIN exome AF: 0.370

Gnomad4 NFE exome AF: 0.428

Gnomad4 OTH exome AF: 0.429

GnomAD4 genome AF: 0.522 AC: 79456 AN: 152104 Hom.: 23252 Cov.: 32 AF XY: 0.511 AC XY: 37990 AN XY: 74348

Gnomad4 AFR AF: 0.806

Gnomad4 AMR AF: 0.508

Gnomad4 ASJ AF: 0.323

Gnomad4 EAS AF: 0.293

Gnomad4 SAS AF: 0.248

Gnomad4 FIN AF: 0.372

Gnomad4 NFE AF: 0.428

Gnomad4 OTH AF: 0.468

Alfa AF: 0.436 Hom.: 12090

Bravo AF: 0.550

Asia WGS AF: 0.348 AC: 1210 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	6.1
DANN	Benign	0.71

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: rs1476792; hg19: chr11-67196237; COSMIC: COSV57048479; COSMIC: COSV57048479;