1-213772666-G-A

Variant names:

• chr1-213772666-G-A
• rs1891059
• ENST00000456240.1:n.144-21718G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The ENST00000456240.1(ENSG00000225233):​n.144-21718G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0413 in 148,344 control chromosomes in the GnomAD database, including 169 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 0.041 (169 hom., cov: 30)
• Consequence: ENSG00000225233 ENST00000456240.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0620
• 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=-0.97).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0413 (6134/148344) while in subpopulation NFE AF = 0.0496 (3347/67442). AF 95% confidence interval is 0.0482. There are 169 homozygotes in GnomAd4. There are 2878 alleles in the male GnomAd4 subpopulation. Median coverage is 30. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 169 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPS6KC1	XR_007058661.1	n.3886+41108G>A		intron_variant	Intron 18 of 18

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000225233	ENST00000456240.1	n.144-21718G>A		intron_variant	Intron 1 of 1	5
ENSG00000225233	ENST00000788945.1	n.439-21718G>A		intron_variant	Intron 3 of 8
ENSG00000225233	ENST00000788946.1	n.444-21718G>A		intron_variant	Intron 3 of 6

Frequencies

GnomAD3 genomes AF: 0.0414 AC: 6132 AN: 148234 Hom.: 169 Cov.: 30

Gnomad AFR AF: 0.0266

Gnomad AMI AF: 0.0850

Gnomad AMR AF: 0.0382

Gnomad ASJ AF: 0.0688

Gnomad EAS AF: 0.000619

Gnomad SAS AF: 0.0240

Gnomad FIN AF: 0.0614

Gnomad MID AF: 0.0915

Gnomad NFE AF: 0.0496

Gnomad OTH AF: 0.0474

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

GnomAD4 genome AF: 0.0413 AC: 6134 AN: 148344 Hom.: 169 Cov.: 30 AF XY: 0.0399 AC XY: 2878 AN XY: 72158

African (AFR) AF: 0.0268 AC: 1080 AN: 40334

American (AMR) AF: 0.0380 AC: 548 AN: 14428

Ashkenazi Jewish (ASJ) AF: 0.0688 AC: 237 AN: 3446

East Asian (EAS) AF: 0.000620 AC: 3 AN: 4836

South Asian (SAS) AF: 0.0236 AC: 109 AN: 4628

European-Finnish (FIN) AF: 0.0614 AC: 612 AN: 9968

Middle Eastern (MID) AF: 0.0833 AC: 24 AN: 288

European-Non Finnish (NFE) AF: 0.0496 AC: 3347 AN: 67442

Other (OTH) AF: 0.0469 AC: 97 AN: 2068

Alfa AF: 0.0381 Hom.: 60

Bravo AF: 0.0401

Asia WGS AF: 0.0140 AC: 47 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.7
DANN	Benign	0.42
PhyloP100		0.062

Splicing

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

Other links and lift over

dbSNP: rs1891059; hg19: chr1-213946009;