rs180535

chr17-59919654-T-C

Variant summary

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

The NM_003161.4(RPS6KB1):c.381+4951T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.142 in 151,926 control chromosomes in the GnomAD database, including 1,680 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 0.14 (1680 hom., cov: 31)
• Consequence: RPS6KB1 NM_003161.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.672

Genes affected

RPS6KB1 (HGNC:10436): (ribosomal protein S6 kinase B1) This gene encodes a member of the ribosomal S6 kinase family of serine/threonine kinases. The encoded protein responds to mTOR (mammalian target of rapamycin) signaling to promote protein synthesis, cell growth, and cell proliferation. Activity of this gene has been associated with human cancer. Alternatively spliced transcript variants have been observed. The use of alternative translation start sites results in isoforms with longer or shorter N-termini which may differ in their subcellular localizations. There are two pseudogenes for this gene on chromosome 17. [provided by RefSeq, Jan 2013]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.161 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RPS6KB1	NM_003161.4	c.381+4951T>C		intron_variant		ENST00000225577.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RPS6KB1	ENST00000225577.9	c.381+4951T>C		intron_variant		1	NM_003161.4	A1

Frequencies

GnomAD3 genomes AF: 0.142 AC: 21591 AN: 151808 Hom.: 1681 Cov.: 31

Gnomad AFR AF: 0.105

Gnomad AMI AF: 0.261

Gnomad AMR AF: 0.162

Gnomad ASJ AF: 0.168

Gnomad EAS AF: 0.0535

Gnomad SAS AF: 0.108

Gnomad FIN AF: 0.157

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.164

Gnomad OTH AF: 0.153

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.142 AC: 21584 AN: 151926 Hom.: 1680 Cov.: 31 AF XY: 0.142 AC XY: 10566 AN XY: 74258

Gnomad4 AFR AF: 0.105

Gnomad4 AMR AF: 0.162

Gnomad4 ASJ AF: 0.168

Gnomad4 EAS AF: 0.0534

Gnomad4 SAS AF: 0.106

Gnomad4 FIN AF: 0.157

Gnomad4 NFE AF: 0.164

Gnomad4 OTH AF: 0.151

Alfa AF: 0.162 Hom.: 2777

Bravo AF: 0.141

Asia WGS AF: 0.0770 AC: 268 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	7.0
Dann	Benign	0.70

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: rs180535; hg19: chr17-57997015;