dbSNP rs2278978: RPS6KA1:c.109-113A>G (chr1-26546754-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_002953.4(RPS6KA1):c.109-113A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.737 in 749,456 control chromosomes in the GnomAD database, including 205,097 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 0.77 ( 45634 hom., cov: 32)

Exomes 𝑓: 0.73 ( 159463 hom. )

Consequence

RPS6KA1
NM_002953.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.334

Publications

14 publications found

Variant links:

Genes affected

RPS6KA1 (HGNC:10430): (ribosomal protein S6 kinase A1) This gene encodes a member of the RSK (ribosomal S6 kinase) family of serine/threonine kinases. This kinase contains 2 nonidentical kinase catalytic domains and phosphorylates various substrates, including members of the mitogen-activated kinase (MAPK) signalling pathway. The activity of this protein has been implicated in controlling cell growth and differentiation. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Jul 2008]

RPS6KA1 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=-0.89).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.883 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002953.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
RPS6KA1	NM_002953.4	MANE Select	c.109-113A>G	intron	N/A	NP_002944.2
RPS6KA1	NM_001006665.2		c.136-113A>G	intron	N/A	NP_001006666.1	Q15418-2
RPS6KA1	NM_001330441.2		c.61-113A>G	intron	N/A	NP_001317370.1	Q15418-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
RPS6KA1	ENST00000374168.7	TSL:1 MANE Select	c.109-113A>G	intron	N/A	ENSP00000363283.2	Q15418-1
RPS6KA1	ENST00000531382.5	TSL:2	c.136-113A>G	intron	N/A	ENSP00000435412.1	Q15418-2
RPS6KA1	ENST00000952528.1		c.109-113A>G	intron	N/A	ENSP00000622587.1

Frequencies

GnomAD3 genomes

AF:

0.770

AC:

117071

AN:

152044

Hom.:

45598

Cov.:

show subpopulations

Gnomad AFR

AF:

0.890

Gnomad AMI

AF:

0.719

Gnomad AMR

AF:

0.685

Gnomad ASJ

AF:

0.639

Gnomad EAS

AF:

0.784

Gnomad SAS

AF:

0.683

Gnomad FIN

AF:

0.754

Gnomad MID

AF:

0.788

Gnomad NFE

AF:

0.731

Gnomad OTH

AF:

0.763

GnomAD4 exome

AF:

0.729

AC:

435237

AN:

597294

Hom.:

159463

AF XY:

0.723

AC XY:

228721

AN XY:

316336

show subpopulations

African (AFR)

AF:

0.891

AC:

14572

AN:

16352

American (AMR)

AF:

0.666

AC:

20350

AN:

30558

Ashkenazi Jewish (ASJ)

AF:

0.664

AC:

11627

AN:

17500

East Asian (EAS)

AF:

0.769

AC:

24695

AN:

32096

South Asian (SAS)

AF:

0.662

AC:

39268

AN:

59290

European-Finnish (FIN)

AF:

0.751

AC:

29001

AN:

38598

Middle Eastern (MID)

AF:

0.709

AC:

2532

AN:

3570

European-Non Finnish (NFE)

AF:

0.734

AC:

270201

AN:

368090

Other (OTH)

AF:

0.736

AC:

22991

AN:

31240

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

5906

11811

17717

23622

29528

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2646

5292

7938

10584

13230

<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:

0.770

AC:

117162

AN:

152162

Hom.:

45634

Cov.:

AF XY:

0.766

AC XY:

56931

AN XY:

74368

show subpopulations

African (AFR)

AF:

0.890

AC:

36979

AN:

41532

American (AMR)

AF:

0.685

AC:

10465

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.639

AC:

2216

AN:

3470

East Asian (EAS)

AF:

0.784

AC:

4050

AN:

5166

South Asian (SAS)

AF:

0.682

AC:

3290

AN:

4826

European-Finnish (FIN)

AF:

0.754

AC:

7993

AN:

10600

Middle Eastern (MID)

AF:

0.793

AC:

233

AN:

294

European-Non Finnish (NFE)

AF:

0.731

AC:

49677

AN:

67972

Other (OTH)

AF:

0.761

AC:

1606

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

1391

2782

4174

5565

6956

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

860

1720

2580

3440

4300

<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:

0.743

Hom.:

143149

Bravo

AF:

0.773

Asia WGS

AF:

0.741

AC:

2576

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

4.4

(source)

DANN

Benign

0.34

PhyloP100

0.33

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over