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 XM_017001024.2(RPS6KC1):​c.3145-40845G>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 XM_017001024.2 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPS6KC1	XM_017001024.2	c.3145-40845G>A		intron_variant	Intron 14 of 14		XP_016856513.2
RPS6KC1	XM_047417936.1	c.2998-40845G>A		intron_variant	Intron 13 of 13		XP_047273892.1
RPS6KC1	XR_007058661.1	n.3255-40845G>A		intron_variant	Intron 14 of 18
RPS6KC1	XR_007058662.1	n.3126-40845G>A		intron_variant	Intron 12 of 13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt

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 v4.3

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;