Genetic Variant NM_003952.3: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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
RPS6KB2	NM_003952.3 link	c.458-365C>A	intron_variant	Intron 5 of 14	ENST00000312629.10	NP_003943.2	Q9UBS0-1
RPS6KB2	XM_047427395.1 link	c.458-365C>A	intron_variant	Intron 5 of 10		XP_047283351.1
RPS6KB2	XM_047427396.1 link	c.458-365C>A	intron_variant	Intron 5 of 9		XP_047283352.1
RPS6KB2	XM_006718656.4 link	c.-401C>A	upstream_gene_variant			XP_006718719.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPS6KB2	ENST00000312629.10 link	c.458-365C>A		intron_variant	Intron 5 of 14	1	NM_003952.3	ENSP00000308413.5		Q9UBS0-1

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 v4.3

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over