11-67429073-C-T

Position:

• chr11-67429073-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_003952.3(RPS6KB2):​c.120-47C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0274 in 1,613,086 control chromosomes in the GnomAD database, including 741 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 0.019 (31 hom., cov: 31)
  • Exomes 𝑓: 0.028 (710 hom.)
• Consequence: RPS6KB2 NM_003952.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.456

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.019 (2884/151840) while in subpopulation NFE AF= 0.0277 (1879/67900). AF 95% confidence interval is 0.0266. There are 31 homozygotes in gnomad4. There are 1433 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 2884 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RPS6KB2	NM_003952.3	c.120-47C>T		intron_variant		ENST00000312629.10
RPS6KB2	XM_047427395.1	c.120-47C>T		intron_variant
RPS6KB2	XM_047427396.1	c.120-47C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RPS6KB2	ENST00000312629.10	c.120-47C>T		intron_variant		1	NM_003952.3	P1

Frequencies

GnomAD3 genomes AF: 0.0190 AC: 2884 AN: 151722 Hom.: 31 Cov.: 31

Gnomad AFR AF: 0.00560

Gnomad AMI AF: 0.0351

Gnomad AMR AF: 0.00938

Gnomad ASJ AF: 0.0230

Gnomad EAS AF: 0.000194

Gnomad SAS AF: 0.00933

Gnomad FIN AF: 0.0421

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0277

Gnomad OTH AF: 0.0130

GnomAD3 exomes AF: 0.0223 AC: 5548 AN: 248882 Hom.: 92 AF XY: 0.0232 AC XY: 3139 AN XY: 135156

Gnomad AFR exome AF: 0.00427

Gnomad AMR exome AF: 0.00869

Gnomad ASJ exome AF: 0.0230

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00723

Gnomad FIN exome AF: 0.0466

Gnomad NFE exome AF: 0.0319

Gnomad OTH exome AF: 0.0210

GnomAD4 exome AF: 0.0282 AC: 41251 AN: 1461246 Hom.: 710 Cov.: 38 AF XY: 0.0275 AC XY: 20024 AN XY: 726844

Gnomad4 AFR exome AF: 0.00442

Gnomad4 AMR exome AF: 0.00935

Gnomad4 ASJ exome AF: 0.0201

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00780

Gnomad4 FIN exome AF: 0.0467

Gnomad4 NFE exome AF: 0.0319

Gnomad4 OTH exome AF: 0.0248

GnomAD4 genome AF: 0.0190 AC: 2884 AN: 151840 Hom.: 31 Cov.: 31 AF XY: 0.0193 AC XY: 1433 AN XY: 74196

Gnomad4 AFR AF: 0.00558

Gnomad4 AMR AF: 0.00936

Gnomad4 ASJ AF: 0.0230

Gnomad4 EAS AF: 0.000194

Gnomad4 SAS AF: 0.00954

Gnomad4 FIN AF: 0.0421

Gnomad4 NFE AF: 0.0277

Gnomad4 OTH AF: 0.0128

Alfa AF: 0.0160 Hom.: 1020

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.9
DANN	Benign	0.65

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

Publications

LitVar

Other links and lift over

dbSNP: rs917570; hg19: chr11-67196544;