11-67432235-C-T

Variant names:

• chr11-67432235-C-T
• rs1638588
• NM_003952.3:c.458-365C>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_003952.3(RPS6KB2):​c.458-365C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000908 in 506,484 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000079 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000096 (0 hom.)
• Consequence: RPS6KB2 NM_003952.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.321
• Publications: 18 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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BS2: High AC in GnomAd4 at 12 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPS6KB2	NM_003952.3	c.458-365C>T		intron_variant	Intron 5 of 14	ENST00000312629.10	NP_003943.2
RPS6KB2	XM_047427395.1	c.458-365C>T		intron_variant	Intron 5 of 10		XP_047283351.1
RPS6KB2	XM_047427396.1	c.458-365C>T		intron_variant	Intron 5 of 9		XP_047283352.1
RPS6KB2	XM_006718656.4	c.-401C>T		upstream_gene_variant			XP_006718719.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPS6KB2	ENST00000312629.10	c.458-365C>T		intron_variant	Intron 5 of 14	1	NM_003952.3	ENSP00000308413.5

Frequencies

GnomAD3 genomes AF: 0.0000789 AC: 12 AN: 152088 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000132

Gnomad OTH AF: 0.000479

GnomAD4 exome AF: 0.0000959 AC: 34 AN: 354396 Hom.: 0 Cov.: 0 AF XY: 0.0000813 AC XY: 16 AN XY: 196812

African (AFR) AF: 0.00 AC: 0 AN: 10528

American (AMR) AF: 0.0000716 AC: 2 AN: 27932

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12974

East Asian (EAS) AF: 0.00 AC: 0 AN: 13566

South Asian (SAS) AF: 0.0000337 AC: 2 AN: 59340

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 16122

Middle Eastern (MID) AF: 0.00161 AC: 5 AN: 3114

European-Non Finnish (NFE) AF: 0.0000934 AC: 18 AN: 192732

Other (OTH) AF: 0.000387 AC: 7 AN: 18088

GnomAD4 genome AF: 0.0000789 AC: 12 AN: 152088 Hom.: 0 Cov.: 33 AF XY: 0.0000942 AC XY: 7 AN XY: 74280

African (AFR) AF: 0.00 AC: 0 AN: 41418

American (AMR) AF: 0.000131 AC: 2 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10590

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000132 AC: 9 AN: 68004

Other (OTH) AF: 0.000479 AC: 1 AN: 2086

Alfa AF: 0.00 Hom.: 17595

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.15
DANN	Benign	0.94
PhyloP100		-0.32

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: rs1638588; hg19: chr11-67199706;