11-64362250-G-A

Variant names:

• chr11-64362250-G-A
• rs538147
• NM_003942.3:c.906+248G>A

Variant summary

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

The NM_003942.3(RPS6KA4):​c.906+248G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.295 in 152,134 control chromosomes in the GnomAD database, including 7,875 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 0.30 (7875 hom., cov: 33)
• Consequence: RPS6KA4 NM_003942.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.240
• Publications: 54 publications found

Genes affected

RPS6KA4 (HGNC:10433): (ribosomal protein S6 kinase A4) This gene encodes a member of the RSK (ribosomal S6 kinase) family of serine/threonine kinases. This kinase contains 2 non-identical kinase catalytic domains and phosphorylates various substrates, including CREB1 and ATF1. The encoded protein can also phosphorylate histone H3 to regulate certain inflammatory genes. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2016]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.373 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003942.3. 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
	RPS6KA4	NM_003942.3	MANE Select	c.906+248G>A		intron	N/A	NP_003933.1
	RPS6KA4	NM_001006944.2		c.906+248G>A		intron	N/A	NP_001006945.1
	RPS6KA4	NM_001300802.2		c.906+248G>A		intron	N/A	NP_001287731.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPS6KA4	ENST00000334205.9	TSL:1 MANE Select	c.906+248G>A		intron	N/A	ENSP00000333896.4
	RPS6KA4	ENST00000528057.5	TSL:1	c.906+248G>A		intron	N/A	ENSP00000435580.1
	RPS6KA4	ENST00000530504.1	TSL:5	c.858+248G>A		intron	N/A	ENSP00000432945.1

Frequencies

GnomAD3 genomes AF: 0.295 AC: 44880 AN: 152016 Hom.: 7875 Cov.: 33

Gnomad AFR AF: 0.101

Gnomad AMI AF: 0.332

Gnomad AMR AF: 0.351

Gnomad ASJ AF: 0.363

Gnomad EAS AF: 0.221

Gnomad SAS AF: 0.382

Gnomad FIN AF: 0.422

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.377

Gnomad OTH AF: 0.277

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.295 AC: 44889 AN: 152134 Hom.: 7875 Cov.: 33 AF XY: 0.300 AC XY: 22290 AN XY: 74366

African (AFR) AF: 0.101 AC: 4207 AN: 41510

American (AMR) AF: 0.352 AC: 5377 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.363 AC: 1258 AN: 3468

East Asian (EAS) AF: 0.221 AC: 1144 AN: 5168

South Asian (SAS) AF: 0.383 AC: 1845 AN: 4822

European-Finnish (FIN) AF: 0.422 AC: 4468 AN: 10586

Middle Eastern (MID) AF: 0.218 AC: 64 AN: 294

European-Non Finnish (NFE) AF: 0.377 AC: 25645 AN: 67970

Other (OTH) AF: 0.274 AC: 578 AN: 2112

Alfa AF: 0.349 Hom.: 40427

Bravo AF: 0.280

Asia WGS AF: 0.312 AC: 1084 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.12
DANN	Benign	0.72
PhyloP100		-0.24
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: rs538147; hg19: chr11-64129722;