rs10274

Positions:

• chr11-67435355-G-A
• chr11-67435355-G-T

Variant summary

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

The NM_003952.3(RPS6KB2):​c.*186G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.389 in 636,066 control chromosomes in the GnomAD database, including 49,983 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 (11236 hom., cov: 33)
  • Exomes 𝑓: 0.39 (38747 hom.)
• Consequence: RPS6KB2 NM_003952.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.701

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=-0.81).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.437 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RPS6KB2	NM_003952.3	c.*186G>A		3_prime_UTR_variant	15/15	ENST00000312629.10
RPS6KB2	XM_006718656.4	c.*186G>A		3_prime_UTR_variant	11/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RPS6KB2	ENST00000312629.10	c.*186G>A		3_prime_UTR_variant	15/15	1	NM_003952.3	P1
RPS6KB2-AS1	ENST00000535922.1	n.45C>T		non_coding_transcript_exon_variant	1/2	3
RPS6KB2	ENST00000525088.5	n.5482G>A		non_coding_transcript_exon_variant	8/8	2
RPS6KB2	ENST00000528964.5			downstream_gene_variant		5

Frequencies

GnomAD3 genomes AF: 0.380 AC: 57729 AN: 151922 Hom.: 11221 Cov.: 33

Gnomad AFR AF: 0.317

Gnomad AMI AF: 0.367

Gnomad AMR AF: 0.447

Gnomad ASJ AF: 0.317

Gnomad EAS AF: 0.293

Gnomad SAS AF: 0.248

Gnomad FIN AF: 0.371

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.425

Gnomad OTH AF: 0.370

GnomAD4 exome AF: 0.392 AC: 189543 AN: 484026 Hom.: 38747 Cov.: 6 AF XY: 0.384 AC XY: 96859 AN XY: 251936

Gnomad4 AFR exome AF: 0.323

Gnomad4 AMR exome AF: 0.507

Gnomad4 ASJ exome AF: 0.311

Gnomad4 EAS exome AF: 0.310

Gnomad4 SAS exome AF: 0.265

Gnomad4 FIN exome AF: 0.376

Gnomad4 NFE exome AF: 0.420

Gnomad4 OTH exome AF: 0.389

GnomAD4 genome AF: 0.380 AC: 57781 AN: 152040 Hom.: 11236 Cov.: 33 AF XY: 0.374 AC XY: 27820 AN XY: 74300

Gnomad4 AFR AF: 0.318

Gnomad4 AMR AF: 0.446

Gnomad4 ASJ AF: 0.317

Gnomad4 EAS AF: 0.293

Gnomad4 SAS AF: 0.247

Gnomad4 FIN AF: 0.371

Gnomad4 NFE AF: 0.425

Gnomad4 OTH AF: 0.368

Alfa AF: 0.400 Hom.: 12665

Bravo AF: 0.391

Asia WGS AF: 0.325 AC: 1130 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.4
DANN	Benign	0.60
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3

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: rs10274; hg19: chr11-67202826;