rs645078

Positions:

• chr11-64367826-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000334205.9(RPS6KA4):​c.1072-306A>C 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 152,120 control chromosomes in the GnomAD database, including 7,850 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 (7850 hom., cov: 32)
• Consequence: RPS6KA4 ENST00000334205.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.774

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.373 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RPS6KA4	NM_003942.3	c.1072-306A>C		intron_variant		ENST00000334205.9	NP_003933.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPS6KA4	ENST00000334205.9	c.1072-306A>C		intron_variant		1	NM_003942.3	ENSP00000333896	P1

Frequencies

GnomAD3 genomes AF: 0.295 AC: 44874 AN: 152002 Hom.: 7850 Cov.: 32

Gnomad AFR AF: 0.102

Gnomad AMI AF: 0.332

Gnomad AMR AF: 0.350

Gnomad ASJ AF: 0.363

Gnomad EAS AF: 0.224

Gnomad SAS AF: 0.376

Gnomad FIN AF: 0.421

Gnomad MID AF: 0.231

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: 44883 AN: 152120 Hom.: 7850 Cov.: 32 AF XY: 0.299 AC XY: 22264 AN XY: 74340

Gnomad4 AFR AF: 0.102

Gnomad4 AMR AF: 0.351

Gnomad4 ASJ AF: 0.363

Gnomad4 EAS AF: 0.225

Gnomad4 SAS AF: 0.377

Gnomad4 FIN AF: 0.421

Gnomad4 NFE AF: 0.377

Gnomad4 OTH AF: 0.273

Alfa AF: 0.354 Hom.: 4646

Bravo AF: 0.280

Asia WGS AF: 0.311 AC: 1083 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.086
DANN	Benign	0.43

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: rs645078; hg19: chr11-64135298;