rs2229714

Variant names:

• chr1-26574217-G-A
• rs2229714
• NM_002953.4:c.*16G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 21 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
RPS6KA1	NM_002953.4	c.*16G>A		3_prime_UTR_variant	Exon 22 of 22	ENST00000374168.7	NP_002944.2
RPS6KA1	NM_001006665.2	c.*16G>A		3_prime_UTR_variant	Exon 21 of 21		NP_001006666.1
RPS6KA1	NM_001330441.2	c.*16G>A		3_prime_UTR_variant	Exon 21 of 21		NP_001317370.1
RPS6KA1	XM_024448871.2	c.*16G>A		3_prime_UTR_variant	Exon 22 of 22		XP_024304639.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPS6KA1	ENST00000374168.7	c.*16G>A		3_prime_UTR_variant	Exon 22 of 22	1	NM_002953.4	ENSP00000363283.2

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

GnomAD2 exomes AF: 0.110 AC: 27687 AN: 251030 AF XY: 0.110

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 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

African (AFR) AF: 0.103 AC: 3442 AN: 33476

American (AMR) AF: 0.0589 AC: 2635 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.113 AC: 2953 AN: 26128

East Asian (EAS) AF: 0.0133 AC: 528 AN: 39698

South Asian (SAS) AF: 0.0653 AC: 5632 AN: 86252

European-Finnish (FIN) AF: 0.169 AC: 9023 AN: 53266

Middle Eastern (MID) AF: 0.110 AC: 634 AN: 5768

European-Non Finnish (NFE) AF: 0.143 AC: 158612 AN: 1111552

Other (OTH) AF: 0.122 AC: 7380 AN: 60382

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

African (AFR) AF: 0.109 AC: 4542 AN: 41528

American (AMR) AF: 0.0787 AC: 1203 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.109 AC: 379 AN: 3472

East Asian (EAS) AF: 0.0140 AC: 72 AN: 5160

South Asian (SAS) AF: 0.0644 AC: 311 AN: 4826

European-Finnish (FIN) AF: 0.172 AC: 1818 AN: 10572

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.149 AC: 10161 AN: 68010

Other (OTH) AF: 0.118 AC: 249 AN: 2110

Alfa AF: 0.133 Hom.: 4077

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
PhyloP100		0.028
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2229714; hg19: chr1-26900708;