Genetic Variant RPS6KB1:c.*126A>G (chr17-59946914-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_003161.4(RPS6KB1):c.*126A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.353 in 1,509,254 control chromosomes in the GnomAD database, including 95,242 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 0.33 ( 8588 hom., cov: 31)

Exomes 𝑓: 0.36 ( 86654 hom. )

Consequence

RPS6KB1
NM_003161.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.97

Publications

61 publications found

Variant links:

Genes affected

RPS6KB1 (HGNC:10436): (ribosomal protein S6 kinase B1) This gene encodes a member of the ribosomal S6 kinase family of serine/threonine kinases. The encoded protein responds to mTOR (mammalian target of rapamycin) signaling to promote protein synthesis, cell growth, and cell proliferation. Activity of this gene has been associated with human cancer. Alternatively spliced transcript variants have been observed. The use of alternative translation start sites results in isoforms with longer or shorter N-termini which may differ in their subcellular localizations. There are two pseudogenes for this gene on chromosome 17. [provided by RefSeq, Jan 2013]

RPS6KB1 Gene-Disease associations (from GenCC):

hypertrophic cardiomyopathy
Inheritance: AD Classification: LIMITED Submitted by: ClinGen

RPS6KB1 links:

ENSG00000267318 (HGNC:):

ENSG00000267318 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=-0.64).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.428 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPS6KB1	NM_003161.4 link	c.*126A>G		3_prime_UTR_variant	Exon 15 of 15	ENST00000225577.9	NP_003152.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPS6KB1	ENST00000225577.9 link	c.*126A>G		3_prime_UTR_variant	Exon 15 of 15	1	NM_003161.4	ENSP00000225577.4
ENSG00000267318	ENST00000591035.1 link	c.149+1396A>G		intron_variant	Intron 2 of 3	3		ENSP00000468280.1

Frequencies

GnomAD3 genomes

AF:

0.332

AC:

50451

AN:

151830

Hom.:

8576

Cov.:

show subpopulations

Gnomad AFR

AF:

0.278

Gnomad AMI

AF:

0.430

Gnomad AMR

AF:

0.329

Gnomad ASJ

AF:

0.303

Gnomad EAS

AF:

0.443

Gnomad SAS

AF:

0.372

Gnomad FIN

AF:

0.332

Gnomad MID

AF:

0.282

Gnomad NFE

AF:

0.355

Gnomad OTH

AF:

0.341

GnomAD4 exome

AF:

0.355

AC:

482096

AN:

1357306

Hom.:

86654

Cov.:

AF XY:

0.356

AC XY:

236837

AN XY:

665100

show subpopulations

African (AFR)

AF:

0.277

AC:

8322

AN:

30080

American (AMR)

AF:

0.305

AC:

9020

AN:

29570

Ashkenazi Jewish (ASJ)

AF:

0.308

AC:

6249

AN:

20274

East Asian (EAS)

AF:

0.459

AC:

17706

AN:

38564

South Asian (SAS)

AF:

0.384

AC:

26583

AN:

69228

European-Finnish (FIN)

AF:

0.333

AC:

15451

AN:

46462

Middle Eastern (MID)

AF:

0.291

AC:

1531

AN:

5268

European-Non Finnish (NFE)

AF:

0.356

AC:

377909

AN:

1061876

Other (OTH)

AF:

0.345

AC:

19325

AN:

55984

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.454

Heterozygous variant carriers

13549

27099

40648

54198

67747

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12514

25028

37542

50056

62570

<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:

0.332

AC:

50499

AN:

151948

Hom.:

8588

Cov.:

AF XY:

0.332

AC XY:

24677

AN XY:

74256

show subpopulations

African (AFR)

AF:

0.278

AC:

11517

AN:

41444

American (AMR)

AF:

0.329

AC:

5014

AN:

15250

Ashkenazi Jewish (ASJ)

AF:

0.303

AC:

1050

AN:

3470

East Asian (EAS)

AF:

0.443

AC:

2287

AN:

5164

South Asian (SAS)

AF:

0.370

AC:

1785

AN:

4824

European-Finnish (FIN)

AF:

0.332

AC:

3488

AN:

10520

Middle Eastern (MID)

AF:

0.299

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.355

AC:

24145

AN:

67966

Other (OTH)

AF:

0.348

AC:

733

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1719

3437

5156

6874

8593

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

510

1020

1530

2040

2550

<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:

0.346

Hom.:

40934

Bravo

AF:

0.327

Asia WGS

AF:

0.441

AC:

1535

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.64

CADD

Benign

9.5

(source)

DANN

Benign

0.64

PhyloP100

3.0

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

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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