Genetic Variant NM_003161.4:c.192-185G>A (chr17-59912499-G-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_003161.4(RPS6KB1):c.192-185G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.495 in 508,614 control chromosomes in the GnomAD database, including 66,203 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 0.56 ( 25953 hom., cov: 32)

Exomes 𝑓: 0.47 ( 40250 hom. )

Consequence

RPS6KB1
NM_003161.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.24

Publications

23 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 links:

RPS29P21 (HGNC:36479): (ribosomal protein S29 pseudogene 21)

RPS29P21 links:

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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=-0.97).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.814 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPS6KB1	NM_003161.4 link	c.192-185G>A		intron_variant	Intron 2 of 14	ENST00000225577.9	NP_003152.1	P23443-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPS6KB1	ENST00000225577.9 link	c.192-185G>A		intron_variant	Intron 2 of 14	1	NM_003161.4	ENSP00000225577.4		P23443-1

Frequencies

GnomAD3 genomes

AF:

0.560

AC:

84998

AN:

151856

Hom.:

25897

Cov.:

show subpopulations

Gnomad AFR

AF:

0.821

Gnomad AMI

AF:

0.497

Gnomad AMR

AF:

0.530

Gnomad ASJ

AF:

0.417

Gnomad EAS

AF:

0.560

Gnomad SAS

AF:

0.427

Gnomad FIN

AF:

0.428

Gnomad MID

AF:

0.554

Gnomad NFE

AF:

0.446

Gnomad OTH

AF:

0.557

GnomAD4 exome

AF:

0.467

AC:

166495

AN:

356640

Hom.:

40250

AF XY:

0.463

AC XY:

86244

AN XY:

186290

show subpopulations

African (AFR)

AF:

0.821

AC:

8870

AN:

10802

American (AMR)

AF:

0.468

AC:

6985

AN:

14924

Ashkenazi Jewish (ASJ)

AF:

0.421

AC:

4565

AN:

10856

East Asian (EAS)

AF:

0.580

AC:

14990

AN:

25830

South Asian (SAS)

AF:

0.425

AC:

12562

AN:

29568

European-Finnish (FIN)

AF:

0.429

AC:

10812

AN:

25186

Middle Eastern (MID)

AF:

0.537

AC:

841

AN:

1566

European-Non Finnish (NFE)

AF:

0.446

AC:

96942

AN:

217416

Other (OTH)

AF:

0.484

AC:

9928

AN:

20492

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

4025

8049

12074

16098

20123

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

786

1572

2358

3144

3930

<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:

0.560

AC:

85115

AN:

151974

Hom.:

25953

Cov.:

AF XY:

0.557

AC XY:

41341

AN XY:

74266

show subpopulations

African (AFR)

AF:

0.821

AC:

34058

AN:

41484

American (AMR)

AF:

0.530

AC:

8078

AN:

15230

Ashkenazi Jewish (ASJ)

AF:

0.417

AC:

1447

AN:

3466

East Asian (EAS)

AF:

0.559

AC:

2889

AN:

5164

South Asian (SAS)

AF:

0.424

AC:

2046

AN:

4820

European-Finnish (FIN)

AF:

0.428

AC:

4513

AN:

10544

Middle Eastern (MID)

AF:

0.572

AC:

167

AN:

292

European-Non Finnish (NFE)

AF:

0.446

AC:

30278

AN:

67952

Other (OTH)

AF:

0.562

AC:

1187

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1744

3488

5231

6975

8719

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

698

1396

2094

2792

3490

<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:

0.477

Hom.:

32822

Bravo

AF:

0.577

Asia WGS

AF:

0.568

AC:

1975

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.97

CADD

Benign

5.9

(source)

DANN

Benign

0.27

PhyloP100

1.2

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