rs8071475

Variant names:

• chr17-59896559-T-C
• rs8071475
• NM_003161.4:c.141+3234T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003161.4(RPS6KB1):​c.141+3234T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.272 in 152,016 control chromosomes in the GnomAD database, including 5,764 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 0.27 (5764 hom., cov: 32)
• Consequence: RPS6KB1 NM_003161.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.493
• Publications: 16 publications found

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]

RPS6KB1 Gene-Disease associations (from GenCC):

• hypertrophic cardiomyopathy

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.315 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPS6KB1	NM_003161.4	c.141+3234T>C		intron_variant	Intron 1 of 14	ENST00000225577.9	NP_003152.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPS6KB1	ENST00000225577.9	c.141+3234T>C		intron_variant	Intron 1 of 14	1	NM_003161.4	ENSP00000225577.4

Frequencies

GnomAD3 genomes AF: 0.272 AC: 41360 AN: 151898 Hom.: 5767 Cov.: 32

Gnomad AFR AF: 0.313

Gnomad AMI AF: 0.333

Gnomad AMR AF: 0.322

Gnomad ASJ AF: 0.283

Gnomad EAS AF: 0.169

Gnomad SAS AF: 0.162

Gnomad FIN AF: 0.251

Gnomad MID AF: 0.398

Gnomad NFE AF: 0.253

Gnomad OTH AF: 0.302

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

GnomAD4 genome AF: 0.272 AC: 41355 AN: 152016 Hom.: 5764 Cov.: 32 AF XY: 0.272 AC XY: 20215 AN XY: 74316

African (AFR) AF: 0.312 AC: 12940 AN: 41446

American (AMR) AF: 0.322 AC: 4906 AN: 15226

Ashkenazi Jewish (ASJ) AF: 0.283 AC: 980 AN: 3466

East Asian (EAS) AF: 0.169 AC: 875 AN: 5180

South Asian (SAS) AF: 0.160 AC: 774 AN: 4830

European-Finnish (FIN) AF: 0.251 AC: 2651 AN: 10562

Middle Eastern (MID) AF: 0.414 AC: 121 AN: 292

European-Non Finnish (NFE) AF: 0.253 AC: 17176 AN: 67998

Other (OTH) AF: 0.298 AC: 628 AN: 2104

Alfa AF: 0.252 Hom.: 2968

Bravo AF: 0.280

Asia WGS AF: 0.182 AC: 634 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	12
DANN	Benign	0.92
PhyloP100		-0.49
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: rs8071475; hg19: chr17-57973920;