Genetic Variant RPS6KB2:c.78+143T>C (chr11-67428766-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_003952.3(RPS6KB2):c.78+143T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.437 in 930,166 control chromosomes in the GnomAD database, including 95,614 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 0.52 ( 23252 hom., cov: 32)

Exomes 𝑓: 0.42 ( 72362 hom. )

Consequence

RPS6KB2
NM_003952.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.275

Publications

29 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.798 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003952.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPS6KB2	NM_003952.3	MANE Select	c.78+143T>C		intron	N/A	NP_003943.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
RPS6KB2	ENST00000312629.10	TSL:1 MANE Select	c.78+143T>C	intron	N/A	ENSP00000308413.5
RPS6KB2	ENST00000525088.5	TSL:2	n.262T>C	non_coding_transcript_exon	Exon 1 of 8
RPS6KB2	ENST00000524934.5	TSL:3	c.78+143T>C	intron	N/A	ENSP00000436811.1

Frequencies

GnomAD3 genomes

AF:

0.522

AC:

79379

AN:

151986

Hom.:

23220

Cov.:

show subpopulations

Gnomad AFR

AF:

0.806

Gnomad AMI

AF:

0.365

Gnomad AMR

AF:

0.509

Gnomad ASJ

AF:

0.323

Gnomad EAS

AF:

0.293

Gnomad SAS

AF:

0.249

Gnomad FIN

AF:

0.372

Gnomad MID

AF:

0.351

Gnomad NFE

AF:

0.428

Gnomad OTH

AF:

0.471

GnomAD4 exome

AF:

0.420

AC:

326684

AN:

778062

Hom.:

72362

Cov.:

AF XY:

0.410

AC XY:

164296

AN XY:

400840

show subpopulations

African (AFR)

AF:

0.808

AC:

15778

AN:

19518

American (AMR)

AF:

0.575

AC:

18664

AN:

32460

Ashkenazi Jewish (ASJ)

AF:

0.319

AC:

5916

AN:

18526

East Asian (EAS)

AF:

0.309

AC:

10195

AN:

33020

South Asian (SAS)

AF:

0.267

AC:

16107

AN:

60416

European-Finnish (FIN)

AF:

0.370

AC:

15768

AN:

42614

Middle Eastern (MID)

AF:

0.381

AC:

1674

AN:

4388

European-Non Finnish (NFE)

AF:

0.428

AC:

226555

AN:

529736

Other (OTH)

AF:

0.429

AC:

16027

AN:

37384

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

11149

22298

33448

44597

55746

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4792

9584

14376

19168

23960

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.522

AC:

79456

AN:

152104

Hom.:

23252

Cov.:

AF XY:

0.511

AC XY:

37990

AN XY:

74348

show subpopulations

African (AFR)

AF:

0.806

AC:

33421

AN:

41486

American (AMR)

AF:

0.508

AC:

7776

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.323

AC:

1121

AN:

3472

East Asian (EAS)

AF:

0.293

AC:

1514

AN:

5166

South Asian (SAS)

AF:

0.248

AC:

1199

AN:

4826

European-Finnish (FIN)

AF:

0.372

AC:

3939

AN:

10594

Middle Eastern (MID)

AF:

0.350

AC:

103

AN:

294

European-Non Finnish (NFE)

AF:

0.428

AC:

29066

AN:

67952

Other (OTH)

AF:

0.468

AC:

986

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1738

3475

5213

6950

8688

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

656

1312

1968

2624

3280

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.491

Hom.:

25414

Bravo

AF:

0.550

Asia WGS

AF:

0.348

AC:

1210

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

6.1

(source)

DANN

Benign

0.71

PhyloP100

-0.28

PromoterAI

-0.018

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over