rs4655303

Variant names:

• chr1-213661300-A-T
• rs4655303
• ENST00000788945.1:n.297-70117A>T

Variant summary

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

The ENST00000788945.1(ENSG00000225233):​n.297-70117A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.39 in 151,996 control chromosomes in the GnomAD database, including 11,717 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 0.39 (11717 hom., cov: 32)
• Consequence: ENSG00000225233 ENST00000788945.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.211
• Publications: 4 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=-0.66).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.445 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPS6KC1	XR_007058661.1	n.3745-70117A>T		intron_variant	Intron 17 of 18

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000225233	ENST00000788945.1	n.297-70117A>T		intron_variant	Intron 2 of 8
ENSG00000225233	ENST00000788946.1	n.302-70117A>T		intron_variant	Intron 2 of 6
ENSG00000225233	ENST00000788947.1	n.457-70117A>T		intron_variant	Intron 2 of 7

Frequencies

GnomAD3 genomes AF: 0.390 AC: 59204 AN: 151878 Hom.: 11704 Cov.: 32

Gnomad AFR AF: 0.442

Gnomad AMI AF: 0.238

Gnomad AMR AF: 0.454

Gnomad ASJ AF: 0.394

Gnomad EAS AF: 0.289

Gnomad SAS AF: 0.365

Gnomad FIN AF: 0.351

Gnomad MID AF: 0.471

Gnomad NFE AF: 0.360

Gnomad OTH AF: 0.406

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

GnomAD4 genome AF: 0.390 AC: 59263 AN: 151996 Hom.: 11717 Cov.: 32 AF XY: 0.390 AC XY: 28942 AN XY: 74290

African (AFR) AF: 0.442 AC: 18315 AN: 41442

American (AMR) AF: 0.454 AC: 6933 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.394 AC: 1369 AN: 3472

East Asian (EAS) AF: 0.289 AC: 1487 AN: 5152

South Asian (SAS) AF: 0.364 AC: 1755 AN: 4816

European-Finnish (FIN) AF: 0.351 AC: 3712 AN: 10568

Middle Eastern (MID) AF: 0.490 AC: 143 AN: 292

European-Non Finnish (NFE) AF: 0.360 AC: 24472 AN: 67964

Other (OTH) AF: 0.408 AC: 860 AN: 2106

Alfa AF: 0.388 Hom.: 1420

Bravo AF: 0.399

Asia WGS AF: 0.331 AC: 1146 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	8.6
DANN	Benign	0.87
PhyloP100		-0.21

Splicing

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

Other links and lift over

dbSNP: rs4655303; hg19: chr1-213834643;