rs538147

Variant summary

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

The NM_003942.3(RPS6KA4):​c.906+248G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.295 in 152,134 control chromosomes in the GnomAD database, including 7,875 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 0.30 ( 7875 hom., cov: 33)

Consequence

RPS6KA4
NM_003942.3 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.240
Variant links:
Genes affected
RPS6KA4 (HGNC:10433): (ribosomal protein S6 kinase A4) This gene encodes a member of the RSK (ribosomal S6 kinase) family of serine/threonine kinases. This kinase contains 2 non-identical kinase catalytic domains and phosphorylates various substrates, including CREB1 and ATF1. The encoded protein can also phosphorylate histone H3 to regulate certain inflammatory genes. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2016]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.92).
BA1
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.373 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RPS6KA4NM_003942.3 linkc.906+248G>A intron_variant Intron 8 of 16 ENST00000334205.9 NP_003933.1 O75676-1A0PJF8

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RPS6KA4ENST00000334205.9 linkc.906+248G>A intron_variant Intron 8 of 16 1 NM_003942.3 ENSP00000333896.4 O75676-1

Frequencies

GnomAD3 genomes
AF:
0.295
AC:
44880
AN:
152016
Hom.:
7875
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.101
Gnomad AMI
AF:
0.332
Gnomad AMR
AF:
0.351
Gnomad ASJ
AF:
0.363
Gnomad EAS
AF:
0.221
Gnomad SAS
AF:
0.382
Gnomad FIN
AF:
0.422
Gnomad MID
AF:
0.234
Gnomad NFE
AF:
0.377
Gnomad OTH
AF:
0.277
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.295
AC:
44889
AN:
152134
Hom.:
7875
Cov.:
33
AF XY:
0.300
AC XY:
22290
AN XY:
74366
show subpopulations
Gnomad4 AFR
AF:
0.101
Gnomad4 AMR
AF:
0.352
Gnomad4 ASJ
AF:
0.363
Gnomad4 EAS
AF:
0.221
Gnomad4 SAS
AF:
0.383
Gnomad4 FIN
AF:
0.422
Gnomad4 NFE
AF:
0.377
Gnomad4 OTH
AF:
0.274
Alfa
AF:
0.358
Hom.:
17534
Bravo
AF:
0.280
Asia WGS
AF:
0.312
AC:
1084
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.92
CADD
Benign
0.12
DANN
Benign
0.72

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: rs538147; hg19: chr11-64129722; API