11-67433348-C-T

Variant names:

• chr11-67433348-C-T
• rs4930427
• NM_003952.3:c.807C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003952.3(RPS6KB2):​c.807C>T​(p.Phe269Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.41 in 1,611,276 control chromosomes in the GnomAD database, including 138,985 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 0.38 (11229 hom., cov: 32)
  • Exomes 𝑓: 0.41 (127756 hom.)
• Consequence: RPS6KB2 NM_003952.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0700
• Publications: 29 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.436 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPS6KB2	NM_003952.3	c.807C>T	p.Phe269Phe	synonymous_variant	Exon 10 of 15	ENST00000312629.10	NP_003943.2
RPS6KB2	XM_047427395.1	c.785C>T	p.Ser262Leu	missense_variant	Exon 10 of 11		XP_047283351.1
RPS6KB2	XM_047427396.1	c.716C>T	p.Ser239Leu	missense_variant	Exon 9 of 10		XP_047283352.1
RPS6KB2	XM_006718656.4	c.207C>T	p.Phe69Phe	synonymous_variant	Exon 6 of 11		XP_006718719.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPS6KB2	ENST00000312629.10	c.807C>T	p.Phe269Phe	synonymous_variant	Exon 10 of 15	1	NM_003952.3	ENSP00000308413.5

Frequencies

GnomAD3 genomes AF: 0.380 AC: 57737 AN: 151968 Hom.: 11215 Cov.: 32

Gnomad AFR AF: 0.318

Gnomad AMI AF: 0.364

Gnomad AMR AF: 0.445

Gnomad ASJ AF: 0.317

Gnomad EAS AF: 0.292

Gnomad SAS AF: 0.247

Gnomad FIN AF: 0.372

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.425

Gnomad OTH AF: 0.371

GnomAD2 exomes AF: 0.394 AC: 98315 AN: 249280 AF XY: 0.385

Gnomad AFR exome AF: 0.321

Gnomad AMR exome AF: 0.564

Gnomad ASJ exome AF: 0.313

Gnomad EAS exome AF: 0.284

Gnomad FIN exome AF: 0.369

Gnomad NFE exome AF: 0.419

Gnomad OTH exome AF: 0.394

GnomAD4 exome AF: 0.413 AC: 603277 AN: 1459192 Hom.: 127756 Cov.: 35 AF XY: 0.407 AC XY: 295830 AN XY: 726030

African (AFR) AF: 0.325 AC: 10870 AN: 33442

American (AMR) AF: 0.551 AC: 24650 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.311 AC: 8118 AN: 26122

East Asian (EAS) AF: 0.307 AC: 12175 AN: 39688

South Asian (SAS) AF: 0.264 AC: 22787 AN: 86244

European-Finnish (FIN) AF: 0.374 AC: 19860 AN: 53170

Middle Eastern (MID) AF: 0.357 AC: 2056 AN: 5764

European-Non Finnish (NFE) AF: 0.432 AC: 478893 AN: 1109734

Other (OTH) AF: 0.396 AC: 23868 AN: 60310

GnomAD4 genome AF: 0.380 AC: 57787 AN: 152084 Hom.: 11229 Cov.: 32 AF XY: 0.374 AC XY: 27824 AN XY: 74338

African (AFR) AF: 0.318 AC: 13209 AN: 41490

American (AMR) AF: 0.445 AC: 6802 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.317 AC: 1100 AN: 3470

East Asian (EAS) AF: 0.292 AC: 1506 AN: 5158

South Asian (SAS) AF: 0.246 AC: 1184 AN: 4820

European-Finnish (FIN) AF: 0.372 AC: 3937 AN: 10590

Middle Eastern (MID) AF: 0.269 AC: 79 AN: 294

European-Non Finnish (NFE) AF: 0.425 AC: 28859 AN: 67952

Other (OTH) AF: 0.369 AC: 780 AN: 2114

Alfa AF: 0.406 Hom.: 12696

Bravo AF: 0.391

Asia WGS AF: 0.325 AC: 1132 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	7.3
DANN	Benign	0.66
PhyloP100		-0.070
RBP_binding_hub_radar		1.0
RBP_regulation_power_radar		2.7
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs4930427; hg19: chr11-67200819; COSMIC: COSV57047270; COSMIC: COSV57047270;