rs1434889

Variant names:

• chr1-213337888-G-A
• rs1434889
• XM_017001024.2:c.3145-40845G>A

Variant summary

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

The XR_007058661.1(RPS6KC1):​n.3255-40845G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.555 in 152,032 control chromosomes in the GnomAD database, including 25,956 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 0.55 (25956 hom., cov: 32)
• Consequence: RPS6KC1 XR_007058661.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.216
• Publications: 1 publications found

Genes affected

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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.689 is higher than 0.05.

Variant Effect in Transcripts

 

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Frequencies

GnomAD3 genomes AF: 0.555 AC: 84332 AN: 151914 Hom.: 25956 Cov.: 32

Gnomad AFR AF: 0.261

Gnomad AMI AF: 0.644

Gnomad AMR AF: 0.586

Gnomad ASJ AF: 0.630

Gnomad EAS AF: 0.629

Gnomad SAS AF: 0.588

Gnomad FIN AF: 0.674

Gnomad MID AF: 0.563

Gnomad NFE AF: 0.694

Gnomad OTH AF: 0.591

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

GnomAD4 genome AF: 0.555 AC: 84339 AN: 152032 Hom.: 25956 Cov.: 32 AF XY: 0.556 AC XY: 41331 AN XY: 74302

African (AFR) AF: 0.260 AC: 10795 AN: 41444

American (AMR) AF: 0.586 AC: 8963 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.630 AC: 2189 AN: 3472

East Asian (EAS) AF: 0.631 AC: 3254 AN: 5160

South Asian (SAS) AF: 0.588 AC: 2833 AN: 4818

European-Finnish (FIN) AF: 0.674 AC: 7112 AN: 10558

Middle Eastern (MID) AF: 0.565 AC: 166 AN: 294

European-Non Finnish (NFE) AF: 0.694 AC: 47201 AN: 67976

Other (OTH) AF: 0.589 AC: 1240 AN: 2106

Alfa AF: 0.651 Hom.: 56559

Bravo AF: 0.535

Asia WGS AF: 0.577 AC: 2012 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.4
DANN	Benign	0.51
PhyloP100		-0.22

Splicing

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

Other links and lift over

dbSNP: rs1434889; hg19: chr1-213511231;