rs1790752

Variant names:

• chr11-67434573-G-A
• rs1790752
• NM_003952.3:c.1156-9G>A

Your query was ambiguous. Multiple possible variants found:

• chr11-67434573-G-A
• chr11-67434573-G-C
• chr11-67434573-G-T

Variant summary

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

The NM_003952.3(RPS6KB2):​c.1156-9G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.433 in 1,596,636 control chromosomes in the GnomAD database, including 156,498 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 0.50 (21085 hom., cov: 33)
  • Exomes 𝑓: 0.43 (135413 hom.)
• Consequence: RPS6KB2 NM_003952.3 intron
• Scores: Splicing: ADA: 0.00003997
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.768
• Publications: 16 publications found

Genes affected

RPS6KB2 (HGNC:10437): (ribosomal protein S6 kinase B2) This gene encodes a member of the RSK (ribosomal S6 kinase) family of serine/threonine kinases. This kinase contains a kinase catalytic domain and phosphorylates the S6 ribosomal protein and eukaryotic translation initiation factor 4B (eIF4B). Phosphorylation of S6 leads to an increase in protein synthesis and cell proliferation. [provided by RefSeq, Jan 2015]

RPS6KB2-AS1 (HGNC:53744): (RPS6KB2 antisense RNA 1)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.734 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003952.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPS6KB2	NM_003952.3	MANE Select	c.1156-9G>A		intron	N/A	NP_003943.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPS6KB2	ENST00000312629.10	TSL:1 MANE Select	c.1156-9G>A		intron	N/A	ENSP00000308413.5
	RPS6KB2	ENST00000531765.2	TSL:3	n.342G>A		non_coding_transcript_exon	Exon 4 of 4
	RPS6KB2	ENST00000525088.5	TSL:2	n.4709-9G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.503 AC: 76435 AN: 151934 Hom.: 21058 Cov.: 33

Gnomad AFR AF: 0.741

Gnomad AMI AF: 0.364

Gnomad AMR AF: 0.499

Gnomad ASJ AF: 0.323

Gnomad EAS AF: 0.292

Gnomad SAS AF: 0.246

Gnomad FIN AF: 0.371

Gnomad MID AF: 0.348

Gnomad NFE AF: 0.427

Gnomad OTH AF: 0.462

GnomAD2 exomes AF: 0.424 AC: 95196 AN: 224608 AF XY: 0.407

Gnomad AFR exome AF: 0.741

Gnomad AMR exome AF: 0.585

Gnomad ASJ exome AF: 0.322

Gnomad EAS exome AF: 0.283

Gnomad FIN exome AF: 0.366

Gnomad NFE exome AF: 0.420

Gnomad OTH exome AF: 0.413

GnomAD4 exome AF: 0.426 AC: 615308 AN: 1444584 Hom.: 135413 Cov.: 32 AF XY: 0.418 AC XY: 300371 AN XY: 718308

African (AFR) AF: 0.750 AC: 24901 AN: 33210

American (AMR) AF: 0.575 AC: 24614 AN: 42796

Ashkenazi Jewish (ASJ) AF: 0.318 AC: 8200 AN: 25790

East Asian (EAS) AF: 0.307 AC: 12025 AN: 39226

South Asian (SAS) AF: 0.264 AC: 22442 AN: 85140

European-Finnish (FIN) AF: 0.370 AC: 17730 AN: 47946

Middle Eastern (MID) AF: 0.377 AC: 2163 AN: 5744

European-Non Finnish (NFE) AF: 0.433 AC: 477941 AN: 1104910

Other (OTH) AF: 0.423 AC: 25292 AN: 59822

GnomAD4 genome AF: 0.503 AC: 76505 AN: 152052 Hom.: 21085 Cov.: 33 AF XY: 0.492 AC XY: 36552 AN XY: 74310

African (AFR) AF: 0.741 AC: 30751 AN: 41476

American (AMR) AF: 0.498 AC: 7619 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.323 AC: 1121 AN: 3468

East Asian (EAS) AF: 0.292 AC: 1510 AN: 5164

South Asian (SAS) AF: 0.245 AC: 1182 AN: 4820

European-Finnish (FIN) AF: 0.371 AC: 3925 AN: 10580

Middle Eastern (MID) AF: 0.347 AC: 102 AN: 294

European-Non Finnish (NFE) AF: 0.427 AC: 28998 AN: 67946

Other (OTH) AF: 0.459 AC: 966 AN: 2106

Alfa AF: 0.432 Hom.: 15483

Bravo AF: 0.529

Asia WGS AF: 0.343 AC: 1194 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.14
DANN	Benign	0.85
PhyloP100		-0.77
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000040
dbscSNV1_RF	Benign	0.0
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: rs1790752; hg19: chr11-67202044; COSMIC: COSV57048486; COSMIC: COSV57048486;