Variant 11-67429073-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_003952.3(RPS6KB2):c.120-47C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0274 in 1,613,086 control chromosomes in the GnomAD database, including 741 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 0.019 ( 31 hom., cov: 31)

Exomes 𝑓: 0.028 ( 710 hom. )

Consequence

RPS6KB2
NM_003952.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.456

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:

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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=-0.87).

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.019 (2884/151840) while in subpopulation NFE AF= 0.0277 (1879/67900). AF 95% confidence interval is 0.0266. There are 31 homozygotes in gnomad4. There are 1433 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High AC in GnomAd4 at 2884 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
RPS6KB2	NM_003952.3 link	c.120-47C>T	intron_variant	ENST00000312629.10	NP_003943.2	Q9UBS0-1
RPS6KB2	XM_047427395.1 link	c.120-47C>T	intron_variant		XP_047283351.1
RPS6KB2	XM_047427396.1 link	c.120-47C>T	intron_variant		XP_047283352.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPS6KB2	ENST00000312629.10 link	c.120-47C>T		intron_variant		1	NM_003952.3	ENSP00000308413.5		Q9UBS0-1

Frequencies

GnomAD3 genomes

AF:

0.0190

AC:

2884

AN:

151722

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00560

Gnomad AMI

AF:

0.0351

Gnomad AMR

AF:

0.00938

Gnomad ASJ

AF:

0.0230

Gnomad EAS

AF:

0.000194

Gnomad SAS

AF:

0.00933

Gnomad FIN

AF:

0.0421

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0277

Gnomad OTH

AF:

0.0130

GnomAD3 exomes

AF:

0.0223

AC:

5548

AN:

248882

Hom.:

AF XY:

0.0232

AC XY:

3139

AN XY:

135156

show subpopulations

Gnomad AFR exome

AF:

0.00427

Gnomad AMR exome

AF:

0.00869

Gnomad ASJ exome

AF:

0.0230

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00723

Gnomad FIN exome

AF:

0.0466

Gnomad NFE exome

AF:

0.0319

Gnomad OTH exome

AF:

0.0210

GnomAD4 exome

AF:

0.0282

AC:

41251

AN:

1461246

Hom.:

710

Cov.:

AF XY:

0.0275

AC XY:

20024

AN XY:

726844

show subpopulations

Gnomad4 AFR exome

AF:

0.00442

Gnomad4 AMR exome

AF:

0.00935

Gnomad4 ASJ exome

AF:

0.0201

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00780

Gnomad4 FIN exome

AF:

0.0467

Gnomad4 NFE exome

AF:

0.0319

Gnomad4 OTH exome

AF:

0.0248

GnomAD4 genome

AF:

0.0190

AC:

2884

AN:

151840

Hom.:

Cov.:

AF XY:

0.0193

AC XY:

1433

AN XY:

74196

show subpopulations

Gnomad4 AFR

AF:

0.00558

Gnomad4 AMR

AF:

0.00936

Gnomad4 ASJ

AF:

0.0230

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.00954

Gnomad4 FIN

AF:

0.0421

Gnomad4 NFE

AF:

0.0277

Gnomad4 OTH

AF:

0.0128

Alfa

AF:

0.0160

Hom.:

1020

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

3.9

DANN

Benign

0.65

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

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