rs2229714

chr1-26574217-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002953.4(RPS6KA1):c.*16G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.13 in 1,613,422 control chromosomes in the GnomAD database, including 14,790 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 0.12 (1330 hom., cov: 31)
  • Exomes 𝑓: 0.13 (13460 hom.)
• Consequence: RPS6KA1 NM_002953.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0280

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.147 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RPS6KA1	NM_002953.4	c.*16G>A		3_prime_UTR_variant	22/22	ENST00000374168.7
RPS6KA1	NM_001006665.2	c.*16G>A		3_prime_UTR_variant	21/21
RPS6KA1	NM_001330441.2	c.*16G>A		3_prime_UTR_variant	21/21
RPS6KA1	XM_024448871.2	c.*16G>A		3_prime_UTR_variant	22/22

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RPS6KA1	ENST00000374168.7	c.*16G>A		3_prime_UTR_variant	22/22	1	NM_002953.4	P1

Frequencies

GnomAD3 genomes AF: 0.124 AC: 18904 AN: 152058 Hom.: 1324 Cov.: 31

Gnomad AFR AF: 0.109

Gnomad AMI AF: 0.191

Gnomad AMR AF: 0.0787

Gnomad ASJ AF: 0.109

Gnomad EAS AF: 0.0139

Gnomad SAS AF: 0.0640

Gnomad FIN AF: 0.172

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.149

Gnomad OTH AF: 0.118

GnomAD3 exomes AF: 0.110 AC: 27687 AN: 251030 Hom.: 1830 AF XY: 0.110 AC XY: 14964 AN XY: 135690

Gnomad AFR exome AF: 0.108

Gnomad AMR exome AF: 0.0547

Gnomad ASJ exome AF: 0.115

Gnomad EAS exome AF: 0.0142

Gnomad SAS exome AF: 0.0643

Gnomad FIN exome AF: 0.169

Gnomad NFE exome AF: 0.144

Gnomad OTH exome AF: 0.115

GnomAD4 exome AF: 0.131 AC: 190839 AN: 1461246 Hom.: 13460 Cov.: 32 AF XY: 0.129 AC XY: 93692 AN XY: 726948

Gnomad4 AFR exome AF: 0.103

Gnomad4 AMR exome AF: 0.0589

Gnomad4 ASJ exome AF: 0.113

Gnomad4 EAS exome AF: 0.0133

Gnomad4 SAS exome AF: 0.0653

Gnomad4 FIN exome AF: 0.169

Gnomad4 NFE exome AF: 0.143

Gnomad4 OTH exome AF: 0.122

GnomAD4 genome AF: 0.124 AC: 18938 AN: 152176 Hom.: 1330 Cov.: 31 AF XY: 0.123 AC XY: 9134 AN XY: 74374

Gnomad4 AFR AF: 0.109

Gnomad4 AMR AF: 0.0787

Gnomad4 ASJ AF: 0.109

Gnomad4 EAS AF: 0.0140

Gnomad4 SAS AF: 0.0644

Gnomad4 FIN AF: 0.172

Gnomad4 NFE AF: 0.149

Gnomad4 OTH AF: 0.118

Alfa AF: 0.136 Hom.: 2556

Bravo AF: 0.116

Asia WGS AF: 0.0520 AC: 180 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
Cadd	Benign	1.9
Dann	Benign	0.71
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Other links and lift over

dbSNP: rs2229714; hg19: chr1-26900708;