1-26546063-A-G

Position:

• chr1-26546063-A-G

Variant summary

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

The NM_002953.4(RPS6KA1):​c.109-804A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.305 in 1,606,354 control chromosomes in the GnomAD database, including 84,393 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 0.36 (10852 hom., cov: 33)
  • Exomes 𝑓: 0.30 (73541 hom.)
• Consequence: RPS6KA1 NM_002953.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.131

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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.745 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RPS6KA1	NM_002953.4	c.109-804A>G		intron_variant		ENST00000374168.7	NP_002944.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPS6KA1	ENST00000374168.7	c.109-804A>G		intron_variant		1	NM_002953.4	ENSP00000363283	P1

Frequencies

GnomAD3 genomes AF: 0.358 AC: 54379 AN: 151950 Hom.: 10849 Cov.: 33

Gnomad AFR AF: 0.475

Gnomad AMI AF: 0.358

Gnomad AMR AF: 0.366

Gnomad ASJ AF: 0.279

Gnomad EAS AF: 0.765

Gnomad SAS AF: 0.511

Gnomad FIN AF: 0.282

Gnomad MID AF: 0.325

Gnomad NFE AF: 0.259

Gnomad OTH AF: 0.357

GnomAD3 exomes AF: 0.372 AC: 86406 AN: 232264 Hom.: 18618 AF XY: 0.368 AC XY: 46892 AN XY: 127330

Gnomad AFR exome AF: 0.474

Gnomad AMR exome AF: 0.418

Gnomad ASJ exome AF: 0.285

Gnomad EAS exome AF: 0.771

Gnomad SAS exome AF: 0.489

Gnomad FIN exome AF: 0.286

Gnomad NFE exome AF: 0.270

Gnomad OTH exome AF: 0.324

GnomAD4 exome AF: 0.300 AC: 435670 AN: 1454284 Hom.: 73541 Cov.: 33 AF XY: 0.303 AC XY: 219223 AN XY: 723592

Gnomad4 AFR exome AF: 0.471

Gnomad4 AMR exome AF: 0.407

Gnomad4 ASJ exome AF: 0.280

Gnomad4 EAS exome AF: 0.752

Gnomad4 SAS exome AF: 0.478

Gnomad4 FIN exome AF: 0.293

Gnomad4 NFE exome AF: 0.260

Gnomad4 OTH exome AF: 0.330

GnomAD4 genome AF: 0.358 AC: 54413 AN: 152070 Hom.: 10852 Cov.: 33 AF XY: 0.363 AC XY: 26982 AN XY: 74338

Gnomad4 AFR AF: 0.475

Gnomad4 AMR AF: 0.365

Gnomad4 ASJ AF: 0.279

Gnomad4 EAS AF: 0.765

Gnomad4 SAS AF: 0.509

Gnomad4 FIN AF: 0.282

Gnomad4 NFE AF: 0.259

Gnomad4 OTH AF: 0.359

Alfa AF: 0.282 Hom.: 1205

Bravo AF: 0.369

Asia WGS AF: 0.608 AC: 2109 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	12
DANN	Benign	0.83

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: rs12723936; hg19: chr1-26872554; COSMIC: COSV64809558; COSMIC: COSV64809558;