rs17706439

Variant names:

• chr1-213682245-G-A
• rs17706439
• ENST00000788945.1:n.297-49172G>A

Variant summary

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

The ENST00000788945.1(ENSG00000225233):​n.297-49172G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.134 in 152,122 control chromosomes in the GnomAD database, including 1,495 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 0.13 (1495 hom., cov: 32)
• Consequence: ENSG00000225233 ENST00000788945.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0390
• Publications: 9 publications found

Genes affected

ENSG00000225233 (HGNC:):

RPS6KC1 (HGNC:10439): (ribosomal protein S6 kinase C1) Sphingosine kinase catalyzes the formation of sphingosine 1 phosphate, a lipid cellular messenger. The protein encoded by this gene can bind to sphingosine kinase and to phosphatidylinositol 3-phosphate, suggesting a role in sphingosine 1 phophate signaling. The encoded protein can also bind to peroxiredoxin-3 and may help transport it to mitochondria. [provided by RefSeq, Mar 2017]

RPS6KC1 Gene-Disease associations (from GenCC):

• periventricular leukomalacia

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.147 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPS6KC1	XR_007058661.1	n.3745-49172G>A		intron_variant	Intron 17 of 18

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000225233	ENST00000788945.1	n.297-49172G>A		intron_variant	Intron 2 of 8
ENSG00000225233	ENST00000788946.1	n.302-49172G>A		intron_variant	Intron 2 of 6
ENSG00000225233	ENST00000788947.1	n.457-49172G>A		intron_variant	Intron 2 of 7

Frequencies

GnomAD3 genomes AF: 0.134 AC: 20414 AN: 152004 Hom.: 1493 Cov.: 32

Gnomad AFR AF: 0.134

Gnomad AMI AF: 0.134

Gnomad AMR AF: 0.0828

Gnomad ASJ AF: 0.119

Gnomad EAS AF: 0.0181

Gnomad SAS AF: 0.0830

Gnomad FIN AF: 0.203

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.149

Gnomad OTH AF: 0.118

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

GnomAD4 genome AF: 0.134 AC: 20422 AN: 152122 Hom.: 1495 Cov.: 32 AF XY: 0.133 AC XY: 9921 AN XY: 74368

African (AFR) AF: 0.134 AC: 5568 AN: 41494

American (AMR) AF: 0.0827 AC: 1264 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.119 AC: 413 AN: 3468

East Asian (EAS) AF: 0.0179 AC: 93 AN: 5184

South Asian (SAS) AF: 0.0831 AC: 401 AN: 4826

European-Finnish (FIN) AF: 0.203 AC: 2144 AN: 10574

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.149 AC: 10135 AN: 67974

Other (OTH) AF: 0.120 AC: 254 AN: 2110

Alfa AF: 0.138 Hom.: 905

Bravo AF: 0.124

Asia WGS AF: 0.0770 AC: 271 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.0
DANN	Benign	0.66
PhyloP100		0.039

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs17706439; hg19: chr1-213855588;