rs1292034

Variant names:

• chr17-59912499-G-A
• rs1292034
• NM_003161.4:c.192-185G>A

Your query was ambiguous. Multiple possible variants found:

• chr17-59912499-G-A
• chr17-59912499-G-C
• chr17-59912499-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.192-185G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.495 in 508,614 control chromosomes in the GnomAD database, including 66,203 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 0.56 (25953 hom., cov: 32)
  • Exomes 𝑓: 0.47 (40250 hom.)
• Consequence: RPS6KB1 NM_003161.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.24
• Publications: 23 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]

RPS29P21 (HGNC:36479): (ribosomal protein S29 pseudogene 21)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.814 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003161.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPS6KB1	NM_003161.4	MANE Select	c.192-185G>A		intron	N/A	NP_003152.1	P23443-1
	RPS6KB1	NM_001272042.2		c.192-185G>A		intron	N/A	NP_001258971.1	P23443-5
	RPS6KB1	NM_001272060.2		c.123-185G>A		intron	N/A	NP_001258989.1	P23443-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPS6KB1	ENST00000225577.9	TSL:1 MANE Select	c.192-185G>A		intron	N/A	ENSP00000225577.4	P23443-1
	RPS6KB1	ENST00000406116.7	TSL:1	c.192-185G>A		intron	N/A	ENSP00000384335.3	P23443-4
	RPS6KB1	ENST00000880476.1		c.192-185G>A		intron	N/A	ENSP00000550535.1

Frequencies

GnomAD3 genomes AF: 0.560 AC: 84998 AN: 151856 Hom.: 25897 Cov.: 32

Gnomad AFR AF: 0.821

Gnomad AMI AF: 0.497

Gnomad AMR AF: 0.530

Gnomad ASJ AF: 0.417

Gnomad EAS AF: 0.560

Gnomad SAS AF: 0.427

Gnomad FIN AF: 0.428

Gnomad MID AF: 0.554

Gnomad NFE AF: 0.446

Gnomad OTH AF: 0.557

GnomAD4 exome AF: 0.467 AC: 166495 AN: 356640 Hom.: 40250 AF XY: 0.463 AC XY: 86244 AN XY: 186290

African (AFR) AF: 0.821 AC: 8870 AN: 10802

American (AMR) AF: 0.468 AC: 6985 AN: 14924

Ashkenazi Jewish (ASJ) AF: 0.421 AC: 4565 AN: 10856

East Asian (EAS) AF: 0.580 AC: 14990 AN: 25830

South Asian (SAS) AF: 0.425 AC: 12562 AN: 29568

European-Finnish (FIN) AF: 0.429 AC: 10812 AN: 25186

Middle Eastern (MID) AF: 0.537 AC: 841 AN: 1566

European-Non Finnish (NFE) AF: 0.446 AC: 96942 AN: 217416

Other (OTH) AF: 0.484 AC: 9928 AN: 20492

GnomAD4 genome AF: 0.560 AC: 85115 AN: 151974 Hom.: 25953 Cov.: 32 AF XY: 0.557 AC XY: 41341 AN XY: 74266

African (AFR) AF: 0.821 AC: 34058 AN: 41484

American (AMR) AF: 0.530 AC: 8078 AN: 15230

Ashkenazi Jewish (ASJ) AF: 0.417 AC: 1447 AN: 3466

East Asian (EAS) AF: 0.559 AC: 2889 AN: 5164

South Asian (SAS) AF: 0.424 AC: 2046 AN: 4820

European-Finnish (FIN) AF: 0.428 AC: 4513 AN: 10544

Middle Eastern (MID) AF: 0.572 AC: 167 AN: 292

European-Non Finnish (NFE) AF: 0.446 AC: 30278 AN: 67952

Other (OTH) AF: 0.562 AC: 1187 AN: 2112

Alfa AF: 0.477 Hom.: 32822

Bravo AF: 0.577

Asia WGS AF: 0.568 AC: 1975 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	5.9
DANN	Benign	0.27
PhyloP100		1.2
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: rs1292034; hg19: chr17-57989860;