chr1-213737151-T-G

Variant names:

• chr1-213737151-T-G
• rs1704198
• ENST00000456240.1:n.143+5593T>G

Variant summary

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

The ENST00000788945.1(ENSG00000225233):​n.438+5593T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.812 in 152,242 control chromosomes in the GnomAD database, including 50,942 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 0.81 (50942 hom., cov: 33)
• Consequence: ENSG00000225233 ENST00000788945.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.79
• Publications: 12 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 (AFR) allele frequency at 95% confidence interval = 0.943 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000788945.1. You can select a different transcript below to see updated ACMG assignments.

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
	ENSG00000225233	ENST00000456240.1	TSL:5	n.143+5593T>G		intron	N/A
	ENSG00000225233	ENST00000788945.1		n.438+5593T>G		intron	N/A
	ENSG00000225233	ENST00000788946.1		n.443+5593T>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.813 AC: 123602 AN: 152124 Hom.: 50906 Cov.: 33

Gnomad AFR AF: 0.950

Gnomad AMI AF: 0.837

Gnomad AMR AF: 0.785

Gnomad ASJ AF: 0.810

Gnomad EAS AF: 0.885

Gnomad SAS AF: 0.726

Gnomad FIN AF: 0.728

Gnomad MID AF: 0.918

Gnomad NFE AF: 0.748

Gnomad OTH AF: 0.814

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

GnomAD4 genome AF: 0.812 AC: 123690 AN: 152242 Hom.: 50942 Cov.: 33 AF XY: 0.811 AC XY: 60347 AN XY: 74430

African (AFR) AF: 0.950 AC: 39502 AN: 41564

American (AMR) AF: 0.784 AC: 11998 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.810 AC: 2813 AN: 3472

East Asian (EAS) AF: 0.884 AC: 4571 AN: 5170

South Asian (SAS) AF: 0.725 AC: 3498 AN: 4826

European-Finnish (FIN) AF: 0.728 AC: 7707 AN: 10590

Middle Eastern (MID) AF: 0.912 AC: 268 AN: 294

European-Non Finnish (NFE) AF: 0.748 AC: 50859 AN: 68004

Other (OTH) AF: 0.811 AC: 1711 AN: 2110

Alfa AF: 0.787 Hom.: 32353

Bravo AF: 0.825

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.2
DANN	Benign	0.85
PhyloP100		-1.8

Splicing

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

Other links and lift over

dbSNP: rs1704198; hg19: chr1-213910494;