rs645078

Variant names:

• chr11-64367826-A-C
• rs645078
• NM_003942.3:c.1072-306A>C

Variant summary

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

The NM_003942.3(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 NM_003942.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.774
• Publications: 31 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=-0.93).
• 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 rank	MANE	Protein	UniProt
RPS6KA4	NM_003942.3	c.1072-306A>C		intron_variant	Intron 9 of 16	ENST00000334205.9	NP_003933.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPS6KA4	ENST00000334205.9	c.1072-306A>C		intron_variant	Intron 9 of 16	1	NM_003942.3	ENSP00000333896.4

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

African (AFR) AF: 0.102 AC: 4249 AN: 41526

American (AMR) AF: 0.351 AC: 5358 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.363 AC: 1261 AN: 3470

East Asian (EAS) AF: 0.225 AC: 1160 AN: 5166

South Asian (SAS) AF: 0.377 AC: 1816 AN: 4822

European-Finnish (FIN) AF: 0.421 AC: 4452 AN: 10574

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.377 AC: 25643 AN: 67966

Other (OTH) AF: 0.273 AC: 578 AN: 2116

Alfa AF: 0.361 Hom.: 6568

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
PhyloP100		-0.77
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: rs645078; hg19: chr11-64135298;