rs282175

Positions:

• chr1-26569311-A-G
• chr1-26569311-A-T

Variant summary

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

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.174

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]

RPS6KA1 (HGNC:):

ACMG classification

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
RPS6KA1	NM_002953.4	c.1591-2138A>G		intron_variant		ENST00000374168.7	NP_002944.2
RPS6KA1	NM_001006665.2	c.1618-2138A>G		intron_variant			NP_001006666.1
RPS6KA1	NM_001330441.2	c.1543-2138A>G		intron_variant			NP_001317370.1
RPS6KA1	XM_024448871.2	c.1315-2138A>G		intron_variant			XP_024304639.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPS6KA1	ENST00000374168.7	c.1591-2138A>G		intron_variant		1	NM_002953.4	ENSP00000363283.2

Frequencies

GnomAD3 genomes AF: 0.346 AC: 52500 AN: 151878 Hom.: 9962 Cov.: 32

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

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

Other links and lift over

dbSNP: rs282175; hg19: chr1-26895802;