dbSNP rs1638588: RPS6KB2:c.458-365C>A (chr11-67432235-C-A) – 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.458-365C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.442 in 506,034 control chromosomes in the GnomAD database, including 55,247 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 ( 23354 hom., cov: 33)

Exomes 𝑓: 0.41 ( 31893 hom. )

Consequence

RPS6KB2
NM_003952.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.321

Publications

18 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=-0.85).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.802 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPS6KB2	NM_003952.3	MANE Select	c.458-365C>A		intron	N/A	NP_003943.2	Q9UBS0-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
RPS6KB2	ENST00000312629.10	TSL:1 MANE Select	c.458-365C>A	intron	N/A	ENSP00000308413.5	Q9UBS0-1
RPS6KB2	ENST00000942409.1		c.458-365C>A	intron	N/A	ENSP00000612468.1
RPS6KB2	ENST00000875118.1		c.464-365C>A	intron	N/A	ENSP00000545177.1

Frequencies

GnomAD3 genomes

AF:

0.523

AC:

79499

AN:

152046

Hom.:

23314

Cov.:

show subpopulations

Gnomad AFR

AF:

0.809

Gnomad AMI

AF:

0.365

Gnomad AMR

AF:

0.506

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:

0.427

Gnomad OTH

AF:

0.470

GnomAD4 exome

AF:

0.407

AC:

144090

AN:

353868

Hom.:

31893

Cov.:

AF XY:

0.390

AC XY:

76610

AN XY:

196500

show subpopulations

African (AFR)

AF:

0.804

AC:

8457

AN:

10514

American (AMR)

AF:

0.575

AC:

16047

AN:

27890

Ashkenazi Jewish (ASJ)

AF:

0.320

AC:

4151

AN:

12956

East Asian (EAS)

AF:

0.294

AC:

3976

AN:

13540

South Asian (SAS)

AF:

0.269

AC:

15932

AN:

59310

European-Finnish (FIN)

AF:

0.364

AC:

5865

AN:

16102

Middle Eastern (MID)

AF:

0.371

AC:

1153

AN:

3104

European-Non Finnish (NFE)

AF:

0.420

AC:

80897

AN:

192406

Other (OTH)

AF:

0.422

AC:

7612

AN:

18046

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

4057

8114

12170

16227

20284

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

508

1016

1524

2032

2540

<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:

0.523

AC:

79586

AN:

152166

Hom.:

23354

Cov.:

AF XY:

0.512

AC XY:

38052

AN XY:

74384

show subpopulations

African (AFR)

AF:

0.809

AC:

33608

AN:

41526

American (AMR)

AF:

0.506

AC:

7728

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.323

AC:

1121

AN:

3472

East Asian (EAS)

AF:

0.293

AC:

1515

AN:

5172

South Asian (SAS)

AF:

0.249

AC:

1200

AN:

4828

European-Finnish (FIN)

AF:

0.372

AC:

3940

AN:

10586

Middle Eastern (MID)

AF:

0.350

AC:

103

AN:

294

European-Non Finnish (NFE)

AF:

0.427

AC:

29054

AN:

67990

Other (OTH)

AF:

0.467

AC:

985

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1742

3485

5227

6970

8712

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

658

1316

1974

2632

3290

<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:

0.483

Hom.:

17595

Bravo

AF:

0.551

Asia WGS

AF:

0.348

AC:

1213

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.12

(source)

DANN

Benign

0.70

PhyloP100

-0.32

Mutation Taster

=22/78

disease causing

(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

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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