chr11-67435355-G-A

Variant names:

• chr11-67435355-G-A
• rs10274
• NM_003952.3:c.*186G>A

Variant summary

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

The NM_003952.3(RPS6KB2):​c.*186G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.389 in 636,066 control chromosomes in the GnomAD database, including 49,983 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 0.38 (11236 hom., cov: 33)
  • Exomes 𝑓: 0.39 (38747 hom.)
• Consequence: RPS6KB2 NM_003952.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.701
• Publications: 23 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)

CORO1B (HGNC:2253): (coronin 1B) Members of the coronin family, such as CORO1B, are WD repeat-containing actin-binding proteins that regulate cell motility (Cai et al., 2005 [PubMed 16027158]).[supplied by OMIM, Mar 2008]

PTPRCAP (HGNC:9667): (protein tyrosine phosphatase receptor type C associated protein) The protein encoded by this gene was identified as a transmembrane phosphoprotein specifically associated with tyrosine phosphatase PTPRC/CD45, a key regulator of T- and B-lymphocyte activation. The interaction with PTPRC may be required for the stable expression of this protein. [provided by RefSeq, Jul 2008]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.437 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPS6KB2	NM_003952.3	MANE Select	c.*186G>A		3_prime_UTR	Exon 15 of 15	NP_003943.2	Q9UBS0-1
	CORO1B	NM_020441.3	MANE Select	c.*3021C>T		downstream_gene	N/A	NP_065174.1	Q9BR76
	PTPRCAP	NM_005608.3	MANE Select	c.*378C>T		downstream_gene	N/A	NP_005599.1	Q14761

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPS6KB2	ENST00000312629.10	TSL:1 MANE Select	c.*186G>A		3_prime_UTR	Exon 15 of 15	ENSP00000308413.5	Q9UBS0-1
	RPS6KB2	ENST00000942409.1		c.*186G>A		3_prime_UTR	Exon 15 of 15	ENSP00000612468.1
	RPS6KB2	ENST00000875118.1		c.*186G>A		3_prime_UTR	Exon 15 of 15	ENSP00000545177.1

Frequencies

GnomAD3 genomes AF: 0.380 AC: 57729 AN: 151922 Hom.: 11221 Cov.: 33

Gnomad AFR AF: 0.317

Gnomad AMI AF: 0.367

Gnomad AMR AF: 0.447

Gnomad ASJ AF: 0.317

Gnomad EAS AF: 0.293

Gnomad SAS AF: 0.248

Gnomad FIN AF: 0.371

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.425

Gnomad OTH AF: 0.370

GnomAD4 exome AF: 0.392 AC: 189543 AN: 484026 Hom.: 38747 Cov.: 6 AF XY: 0.384 AC XY: 96859 AN XY: 251936

African (AFR) AF: 0.323 AC: 4161 AN: 12902

American (AMR) AF: 0.507 AC: 8652 AN: 17062

Ashkenazi Jewish (ASJ) AF: 0.311 AC: 4276 AN: 13736

East Asian (EAS) AF: 0.310 AC: 9381 AN: 30272

South Asian (SAS) AF: 0.265 AC: 11990 AN: 45190

European-Finnish (FIN) AF: 0.376 AC: 11057 AN: 29402

Middle Eastern (MID) AF: 0.355 AC: 730 AN: 2054

European-Non Finnish (NFE) AF: 0.420 AC: 128782 AN: 306392

Other (OTH) AF: 0.389 AC: 10514 AN: 27016

GnomAD4 genome AF: 0.380 AC: 57781 AN: 152040 Hom.: 11236 Cov.: 33 AF XY: 0.374 AC XY: 27820 AN XY: 74300

African (AFR) AF: 0.318 AC: 13184 AN: 41472

American (AMR) AF: 0.446 AC: 6814 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.317 AC: 1100 AN: 3472

East Asian (EAS) AF: 0.293 AC: 1511 AN: 5164

South Asian (SAS) AF: 0.247 AC: 1189 AN: 4820

European-Finnish (FIN) AF: 0.371 AC: 3925 AN: 10572

Middle Eastern (MID) AF: 0.279 AC: 82 AN: 294

European-Non Finnish (NFE) AF: 0.425 AC: 28867 AN: 67958

Other (OTH) AF: 0.368 AC: 776 AN: 2108

Alfa AF: 0.401 Hom.: 22415

Bravo AF: 0.391

Asia WGS AF: 0.325 AC: 1130 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.4
DANN	Benign	0.60
PhyloP100		-0.70
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3
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: rs10274; hg19: chr11-67202826;