rs180531

Variant names:

• chr17-59925997-G-A
• rs180531
• NM_003161.4:c.382-438G>A

Your query was ambiguous. Multiple possible variants found:

• chr17-59925997-G-A
• chr17-59925997-G-C
• chr17-59925997-G-T

Variant summary

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

The NM_003161.4(RPS6KB1):​c.382-438G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.79 in 151,966 control chromosomes in the GnomAD database, including 48,242 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 0.79 (48242 hom., cov: 30)
• Consequence: RPS6KB1 NM_003161.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0730
• Publications: 5 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.939 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPS6KB1	NM_003161.4	c.382-438G>A		intron_variant	Intron 4 of 14	ENST00000225577.9	NP_003152.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPS6KB1	ENST00000225577.9	c.382-438G>A		intron_variant	Intron 4 of 14	1	NM_003161.4	ENSP00000225577.4

Frequencies

GnomAD3 genomes AF: 0.790 AC: 119965 AN: 151848 Hom.: 48191 Cov.: 30

Gnomad AFR AF: 0.946

Gnomad AMI AF: 0.751

Gnomad AMR AF: 0.715

Gnomad ASJ AF: 0.772

Gnomad EAS AF: 0.594

Gnomad SAS AF: 0.750

Gnomad FIN AF: 0.740

Gnomad MID AF: 0.908

Gnomad NFE AF: 0.738

Gnomad OTH AF: 0.810

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

GnomAD4 genome AF: 0.790 AC: 120071 AN: 151966 Hom.: 48242 Cov.: 30 AF XY: 0.786 AC XY: 58386 AN XY: 74258

African (AFR) AF: 0.946 AC: 39268 AN: 41492

American (AMR) AF: 0.714 AC: 10881 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.772 AC: 2680 AN: 3470

East Asian (EAS) AF: 0.593 AC: 3058 AN: 5156

South Asian (SAS) AF: 0.749 AC: 3605 AN: 4812

European-Finnish (FIN) AF: 0.740 AC: 7797 AN: 10536

Middle Eastern (MID) AF: 0.905 AC: 266 AN: 294

European-Non Finnish (NFE) AF: 0.738 AC: 50120 AN: 67954

Other (OTH) AF: 0.812 AC: 1711 AN: 2106

Alfa AF: 0.757 Hom.: 14641

Bravo AF: 0.791

Asia WGS AF: 0.725 AC: 2522 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.83
DANN	Benign	0.52
PhyloP100		0.073
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: rs180531; hg19: chr17-58003358;