1-213661300-A-T

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.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000225233	ENST00000788945.1		n.297-70117A>T		intron	N/A
	ENSG00000225233	ENST00000788946.1		n.302-70117A>T		intron	N/A
	ENSG00000225233	ENST00000788947.1		n.457-70117A>T		intron	N/A

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 v4.9

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;