11-67429073-C-G

Variant names:

• chr11-67429073-C-G
• rs917570
• NM_003952.3:c.120-47C>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 18 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]

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
RPS6KB2	NM_003952.3	c.120-47C>G		intron_variant	Intron 2 of 14	ENST00000312629.10	NP_003943.2
RPS6KB2	XM_047427395.1	c.120-47C>G		intron_variant	Intron 2 of 10		XP_047283351.1
RPS6KB2	XM_047427396.1	c.120-47C>G		intron_variant	Intron 2 of 9		XP_047283352.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPS6KB2	ENST00000312629.10	c.120-47C>G		intron_variant	Intron 2 of 14	1	NM_003952.3	ENSP00000308413.5

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

GnomAD2 exomes AF: 0.303 AC: 75497 AN: 248882 AF XY: 0.310

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 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

African (AFR) AF: 0.192 AC: 6437 AN: 33468

American (AMR) AF: 0.191 AC: 8535 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.275 AC: 7180 AN: 26132

East Asian (EAS) AF: 0.139 AC: 5530 AN: 39694

South Asian (SAS) AF: 0.232 AC: 20045 AN: 86248

European-Finnish (FIN) AF: 0.312 AC: 16576 AN: 53188

Middle Eastern (MID) AF: 0.340 AC: 1962 AN: 5766

European-Non Finnish (NFE) AF: 0.416 AC: 462319 AN: 1110782

Other (OTH) AF: 0.349 AC: 21071 AN: 60344

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

African (AFR) AF: 0.196 AC: 8088 AN: 41370

American (AMR) AF: 0.237 AC: 3610 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.277 AC: 963 AN: 3472

East Asian (EAS) AF: 0.139 AC: 717 AN: 5140

South Asian (SAS) AF: 0.217 AC: 1043 AN: 4816

European-Finnish (FIN) AF: 0.302 AC: 3170 AN: 10512

Middle Eastern (MID) AF: 0.265 AC: 78 AN: 294

European-Non Finnish (NFE) AF: 0.407 AC: 27611 AN: 67876

Other (OTH) AF: 0.301 AC: 634 AN: 2106

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
PhyloP100		-0.46
RBP_binding_hub_radar		1.0
RBP_regulation_power_radar		2.3
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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