rs1638588

chr11-67432235-C-Achr11-67432235-C-Gchr11-67432235-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.458-365C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.442 in 506,034 control chromosomes in the GnomAD database, including 55,247 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 (23354 hom., cov: 33)
  • Exomes 𝑓: 0.41 (31893 hom.)
• Consequence: RPS6KB2 NM_003952.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.321

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]

RPS6KB2-AS1 (HGNC:53744): (RPS6KB2 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.802 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RPS6KB2	NM_003952.3	c.458-365C>A		intron_variant		ENST00000312629.10
RPS6KB2	XM_047427395.1	c.458-365C>A		intron_variant
RPS6KB2	XM_047427396.1	c.458-365C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RPS6KB2	ENST00000312629.10	c.458-365C>A		intron_variant		1	NM_003952.3	P1
RPS6KB2-AS1	ENST00000535922.1	n.344-742G>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.523 AC: 79499 AN: 152046 Hom.: 23314 Cov.: 33

Gnomad AFR AF: 0.809

Gnomad AMI AF: 0.365

Gnomad AMR AF: 0.506

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: 0.427

Gnomad OTH AF: 0.470

GnomAD4 exome AF: 0.407 AC: 144090 AN: 353868 Hom.: 31893 Cov.: 0 AF XY: 0.390 AC XY: 76610 AN XY: 196500

Gnomad4 AFR exome AF: 0.804

Gnomad4 AMR exome AF: 0.575

Gnomad4 ASJ exome AF: 0.320

Gnomad4 EAS exome AF: 0.294

Gnomad4 SAS exome AF: 0.269

Gnomad4 FIN exome AF: 0.364

Gnomad4 NFE exome AF: 0.420

Gnomad4 OTH exome AF: 0.422

GnomAD4 genome AF: 0.523 AC: 79586 AN: 152166 Hom.: 23354 Cov.: 33 AF XY: 0.512 AC XY: 38052 AN XY: 74384

Gnomad4 AFR AF: 0.809

Gnomad4 AMR AF: 0.506

Gnomad4 ASJ AF: 0.323

Gnomad4 EAS AF: 0.293

Gnomad4 SAS AF: 0.249

Gnomad4 FIN AF: 0.372

Gnomad4 NFE AF: 0.427

Gnomad4 OTH AF: 0.467

Alfa AF: 0.401 Hom.: 5495

Bravo AF: 0.551

Asia WGS AF: 0.348 AC: 1213 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	0.12
Dann	Benign	0.70

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: rs1638588; hg19: chr11-67199706; COSMIC: COSV57050295; COSMIC: COSV57050295;