Genetic Variant RPS6KB2:c.906+90C>T (chr11-67433537-C-T) – 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.906+90C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.421 in 998,264 control chromosomes in the GnomAD database, including 95,146 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 ( 21201 hom., cov: 33)

Exomes 𝑓: 0.41 ( 73945 hom. )

Consequence

RPS6KB2
NM_003952.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.74

Publications

11 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:

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

RPS6KB2-AS1 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=-0.88).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.737 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
RPS6KB2	NM_003952.3 link	c.906+90C>T	intron_variant	Intron 10 of 14	ENST00000312629.10	NP_003943.2	Q9UBS0-1
RPS6KB2	XM_047427395.1 link	c.884+90C>T	intron_variant	Intron 10 of 10		XP_047283351.1
RPS6KB2	XM_006718656.4 link	c.306+90C>T	intron_variant	Intron 6 of 10		XP_006718719.1
RPS6KB2	XM_047427396.1 link	c.815+90C>T	intron_variant	Intron 9 of 9		XP_047283352.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPS6KB2	ENST00000312629.10 link	c.906+90C>T		intron_variant	Intron 10 of 14	1	NM_003952.3	ENSP00000308413.5		Q9UBS0-1

Frequencies

GnomAD3 genomes

AF:

0.504

AC:

76644

AN:

152006

Hom.:

21173

Cov.:

show subpopulations

Gnomad AFR

AF:

0.744

Gnomad AMI

AF:

0.366

Gnomad AMR

AF:

0.499

Gnomad ASJ

AF:

0.323

Gnomad EAS

AF:

0.293

Gnomad SAS

AF:

0.249

Gnomad FIN

AF:

0.371

Gnomad MID

AF:

0.348

Gnomad NFE

AF:

0.427

Gnomad OTH

AF:

0.461

GnomAD4 exome

AF:

0.406

AC:

343817

AN:

846140

Hom.:

73945

AF XY:

0.398

AC XY:

176013

AN XY:

442652

show subpopulations

African (AFR)

AF:

0.743

AC:

15935

AN:

21434

American (AMR)

AF:

0.577

AC:

22602

AN:

39184

Ashkenazi Jewish (ASJ)

AF:

0.319

AC:

6797

AN:

21290

East Asian (EAS)

AF:

0.307

AC:

10967

AN:

35758

South Asian (SAS)

AF:

0.264

AC:

19092

AN:

72362

European-Finnish (FIN)

AF:

0.373

AC:

17443

AN:

46784

Middle Eastern (MID)

AF:

0.372

AC:

1676

AN:

4502

European-Non Finnish (NFE)

AF:

0.412

AC:

232595

AN:

564652

Other (OTH)

AF:

0.416

AC:

16710

AN:

40174

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

10837

21673

32510

43346

54183

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4696

9392

14088

18784

23480

<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:

0.504

AC:

76716

AN:

152124

Hom.:

21201

Cov.:

AF XY:

0.493

AC XY:

36652

AN XY:

74366

show subpopulations

African (AFR)

AF:

0.744

AC:

30883

AN:

41510

American (AMR)

AF:

0.498

AC:

7625

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.323

AC:

1121

AN:

3472

East Asian (EAS)

AF:

0.294

AC:

1517

AN:

5168

South Asian (SAS)

AF:

0.248

AC:

1195

AN:

4820

European-Finnish (FIN)

AF:

0.371

AC:

3934

AN:

10590

Middle Eastern (MID)

AF:

0.347

AC:

102

AN:

294

European-Non Finnish (NFE)

AF:

0.427

AC:

29038

AN:

67948

Other (OTH)

AF:

0.458

AC:

968

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1851

3702

5554

7405

9256

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

650

1300

1950

2600

3250

<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:

0.520

Hom.:

9956

Bravo

AF:

0.530

Asia WGS

AF:

0.344

AC:

1198

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.35

(source)

DANN

Benign

0.80

PhyloP100

-2.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over