chr11-67433537-C-T

Position:

• chr11-67433537-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.906+90C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.421 in 998,264 control chromosomes in the GnomAD database, including 95,146 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 0.50 (21201 hom., cov: 33)
  • Exomes 𝑓: 0.41 (73945 hom.)
• Consequence: RPS6KB2 NM_003952.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.74

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.737 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RPS6KB2	NM_003952.3	c.906+90C>T		intron_variant		ENST00000312629.10	NP_003943.2
RPS6KB2	XM_047427395.1	c.884+90C>T		intron_variant			XP_047283351.1
RPS6KB2	XM_006718656.4	c.306+90C>T		intron_variant			XP_006718719.1
RPS6KB2	XM_047427396.1	c.815+90C>T		intron_variant			XP_047283352.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPS6KB2	ENST00000312629.10	c.906+90C>T		intron_variant		1	NM_003952.3	ENSP00000308413.5

Frequencies

GnomAD3 genomes AF: 0.504 AC: 76644 AN: 152006 Hom.: 21173 Cov.: 33

Gnomad AFR AF: 0.744

Gnomad AMI AF: 0.366

Gnomad AMR AF: 0.499

Gnomad ASJ AF: 0.323

Gnomad EAS AF: 0.293

Gnomad SAS AF: 0.249

Gnomad FIN AF: 0.371

Gnomad MID AF: 0.348

Gnomad NFE AF: 0.427

Gnomad OTH AF: 0.461

GnomAD4 exome AF: 0.406 AC: 343817 AN: 846140 Hom.: 73945 AF XY: 0.398 AC XY: 176013 AN XY: 442652

Gnomad4 AFR exome AF: 0.743

Gnomad4 AMR exome AF: 0.577

Gnomad4 ASJ exome AF: 0.319

Gnomad4 EAS exome AF: 0.307

Gnomad4 SAS exome AF: 0.264

Gnomad4 FIN exome AF: 0.373

Gnomad4 NFE exome AF: 0.412

Gnomad4 OTH exome AF: 0.416

GnomAD4 genome AF: 0.504 AC: 76716 AN: 152124 Hom.: 21201 Cov.: 33 AF XY: 0.493 AC XY: 36652 AN XY: 74366

Gnomad4 AFR AF: 0.744

Gnomad4 AMR AF: 0.498

Gnomad4 ASJ AF: 0.323

Gnomad4 EAS AF: 0.294

Gnomad4 SAS AF: 0.248

Gnomad4 FIN AF: 0.371

Gnomad4 NFE AF: 0.427

Gnomad4 OTH AF: 0.458

Alfa AF: 0.462 Hom.: 4848

Bravo AF: 0.530

Asia WGS AF: 0.344 AC: 1198 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.35
DANN	Benign	0.80
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs1790753; hg19: chr11-67201008; COSMIC: COSV57051429; COSMIC: COSV57051429;