rs282175

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002953.4(RPS6KA1):​c.1591-2138A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.346 in 151,996 control chromosomes in the GnomAD database, including 9,965 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 0.35 ( 9965 hom., cov: 32)

Consequence

RPS6KA1
NM_002953.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.174
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.99).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.734 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
RPS6KA1NM_002953.4 linkuse as main transcriptc.1591-2138A>G intron_variant ENST00000374168.7 NP_002944.2 Q15418-1
RPS6KA1NM_001006665.2 linkuse as main transcriptc.1618-2138A>G intron_variant NP_001006666.1 Q15418-2
RPS6KA1NM_001330441.2 linkuse as main transcriptc.1543-2138A>G intron_variant NP_001317370.1 Q15418-4
RPS6KA1XM_024448871.2 linkuse as main transcriptc.1315-2138A>G intron_variant XP_024304639.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
RPS6KA1ENST00000374168.7 linkuse as main transcriptc.1591-2138A>G intron_variant 1 NM_002953.4 ENSP00000363283.2 Q15418-1

Frequencies

GnomAD3 genomes
AF:
0.346
AC:
52500
AN:
151878
Hom.:
9962
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.414
Gnomad AMI
AF:
0.347
Gnomad AMR
AF:
0.360
Gnomad ASJ
AF:
0.303
Gnomad EAS
AF:
0.755
Gnomad SAS
AF:
0.570
Gnomad FIN
AF:
0.284
Gnomad MID
AF:
0.326
Gnomad NFE
AF:
0.266
Gnomad OTH
AF:
0.350
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.346
AC:
52534
AN:
151996
Hom.:
9965
Cov.:
32
AF XY:
0.352
AC XY:
26181
AN XY:
74274
show subpopulations
Gnomad4 AFR
AF:
0.414
Gnomad4 AMR
AF:
0.360
Gnomad4 ASJ
AF:
0.303
Gnomad4 EAS
AF:
0.754
Gnomad4 SAS
AF:
0.568
Gnomad4 FIN
AF:
0.284
Gnomad4 NFE
AF:
0.265
Gnomad4 OTH
AF:
0.354
Alfa
AF:
0.296
Hom.:
1746
Bravo
AF:
0.353
Asia WGS
AF:
0.627
AC:
2177
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.99
CADD
Benign
3.2
DANN
Benign
0.50

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs282175; hg19: chr1-26895802; API