rs1476792

Variant names:

• chr11-67428766-T-C
• rs1476792
• NM_003952.3:c.78+143T>C

Your query was ambiguous. Multiple possible variants found:

• chr11-67428766-T-C
• chr11-67428766-T-G

Variant summary

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

The NM_003952.3(RPS6KB2):​c.78+143T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.437 in 930,166 control chromosomes in the GnomAD database, including 95,614 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 0.52 (23252 hom., cov: 32)
  • Exomes 𝑓: 0.42 (72362 hom.)
• Consequence: RPS6KB2 NM_003952.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.275
• Publications: 29 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.798 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPS6KB2	NM_003952.3	c.78+143T>C		intron_variant	Intron 1 of 14	ENST00000312629.10	NP_003943.2
RPS6KB2	XM_047427395.1	c.78+143T>C		intron_variant	Intron 1 of 10		XP_047283351.1
RPS6KB2	XM_047427396.1	c.78+143T>C		intron_variant	Intron 1 of 9		XP_047283352.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPS6KB2	ENST00000312629.10	c.78+143T>C		intron_variant	Intron 1 of 14	1	NM_003952.3	ENSP00000308413.5

Frequencies

GnomAD3 genomes AF: 0.522 AC: 79379 AN: 151986 Hom.: 23220 Cov.: 32

Gnomad AFR AF: 0.806

Gnomad AMI AF: 0.365

Gnomad AMR AF: 0.509

Gnomad ASJ AF: 0.323

Gnomad EAS AF: 0.293

Gnomad SAS AF: 0.249

Gnomad FIN AF: 0.372

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.428

Gnomad OTH AF: 0.471

GnomAD4 exome AF: 0.420 AC: 326684 AN: 778062 Hom.: 72362 Cov.: 10 AF XY: 0.410 AC XY: 164296 AN XY: 400840

African (AFR) AF: 0.808 AC: 15778 AN: 19518

American (AMR) AF: 0.575 AC: 18664 AN: 32460

Ashkenazi Jewish (ASJ) AF: 0.319 AC: 5916 AN: 18526

East Asian (EAS) AF: 0.309 AC: 10195 AN: 33020

South Asian (SAS) AF: 0.267 AC: 16107 AN: 60416

European-Finnish (FIN) AF: 0.370 AC: 15768 AN: 42614

Middle Eastern (MID) AF: 0.381 AC: 1674 AN: 4388

European-Non Finnish (NFE) AF: 0.428 AC: 226555 AN: 529736

Other (OTH) AF: 0.429 AC: 16027 AN: 37384

GnomAD4 genome AF: 0.522 AC: 79456 AN: 152104 Hom.: 23252 Cov.: 32 AF XY: 0.511 AC XY: 37990 AN XY: 74348

African (AFR) AF: 0.806 AC: 33421 AN: 41486

American (AMR) AF: 0.508 AC: 7776 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.323 AC: 1121 AN: 3472

East Asian (EAS) AF: 0.293 AC: 1514 AN: 5166

South Asian (SAS) AF: 0.248 AC: 1199 AN: 4826

European-Finnish (FIN) AF: 0.372 AC: 3939 AN: 10594

Middle Eastern (MID) AF: 0.350 AC: 103 AN: 294

European-Non Finnish (NFE) AF: 0.428 AC: 29066 AN: 67952

Other (OTH) AF: 0.468 AC: 986 AN: 2108

Alfa AF: 0.491 Hom.: 25414

Bravo AF: 0.550

Asia WGS AF: 0.348 AC: 1210 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	6.1
DANN	Benign	0.71
PhyloP100		-0.28
PromoterAI		-0.018	Neutral
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: rs1476792; hg19: chr11-67196237; COSMIC: COSV57048479; COSMIC: COSV57048479;