Variant rs1790752 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_003952.3(RPS6KB2):c.1156-9G>A variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.433 in 1,596,636 control chromosomes in the GnomAD database, including 156,498 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 ( 21085 hom., cov: 33)

Exomes 𝑓: 0.43 ( 135413 hom. )

Consequence

RPS6KB2
NM_003952.3 splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00003997

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.768

Variant links:

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 links:

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

RPS6KB2-AS1 links:

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ACMG classification

Classification made for transcript

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 = 0.734 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RPS6KB2	NM_003952.3 linkuse as main transcript	c.1156-9G>A		splice_polypyrimidine_tract_variant, intron_variant		ENST00000312629.10
RPS6KB2	XM_006718656.4 linkuse as main transcript	c.556-9G>A		splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RPS6KB2	ENST00000312629.10 linkuse as main transcript	c.1156-9G>A		splice_polypyrimidine_tract_variant, intron_variant		1	NM_003952.3	P1	Q9UBS0-1
RPS6KB2-AS1	ENST00000535922.1 linkuse as main transcript	n.343+484C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.503

AC:

76435

AN:

151934

Hom.:

21058

Cov.:

show subpopulations

Gnomad AFR

AF:

0.741

Gnomad AMI

AF:

0.364

Gnomad AMR

AF:

0.499

Gnomad ASJ

AF:

0.323

Gnomad EAS

AF:

0.292

Gnomad SAS

AF:

0.246

Gnomad FIN

AF:

0.371

Gnomad MID

AF:

0.348

Gnomad NFE

AF:

0.427

Gnomad OTH

AF:

0.462

GnomAD3 exomes

AF:

0.424

AC:

95196

AN:

224608

Hom.:

21835

AF XY:

0.407

AC XY:

50188

AN XY:

123364

show subpopulations

Gnomad AFR exome

AF:

0.741

Gnomad AMR exome

AF:

0.585

Gnomad ASJ exome

AF:

0.322

Gnomad EAS exome

AF:

0.283

Gnomad SAS exome

AF:

0.258

Gnomad FIN exome

AF:

0.366

Gnomad NFE exome

AF:

0.420

Gnomad OTH exome

AF:

0.413

GnomAD4 exome

AF:

0.426

AC:

615308

AN:

1444584

Hom.:

135413

Cov.:

AF XY:

0.418

AC XY:

300371

AN XY:

718308

show subpopulations

Gnomad4 AFR exome

AF:

0.750

Gnomad4 AMR exome

AF:

0.575

Gnomad4 ASJ exome

AF:

0.318

Gnomad4 EAS exome

AF:

0.307

Gnomad4 SAS exome

AF:

0.264

Gnomad4 FIN exome

AF:

0.370

Gnomad4 NFE exome

AF:

0.433

Gnomad4 OTH exome

AF:

0.423

GnomAD4 genome

AF:

0.503

AC:

76505

AN:

152052

Hom.:

21085

Cov.:

AF XY:

0.492

AC XY:

36552

AN XY:

74310

show subpopulations

Gnomad4 AFR

AF:

0.741

Gnomad4 AMR

AF:

0.498

Gnomad4 ASJ

AF:

0.323

Gnomad4 EAS

AF:

0.292

Gnomad4 SAS

AF:

0.245

Gnomad4 FIN

AF:

0.371

Gnomad4 NFE

AF:

0.427

Gnomad4 OTH

AF:

0.459

Alfa

AF:

0.408

Hom.:

10567

Bravo

AF:

0.529

Asia WGS

AF:

0.343

AC:

1194

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

0.14

Dann

Benign

0.85

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000040

dbscSNV1_RF

Benign

0.0

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over