Genetic Variant ENST00000788945.1:n.297-3502A>G (chr1-213727915-A-G) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is . The variant received -10 ACMG points: 0P and 10B. BP4_ModerateBA1

The ENST00000788945.1(ENSG00000225233):n.297-3502A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.283 in 152,056 control chromosomes in the GnomAD database, including 6,913 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 0.28 ( 6913 hom., cov: 32)

Consequence

ENSG00000225233
ENST00000788945.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.267

Publications

2 publications found

Variant links:

Genes affected

ENSG00000225233 (HGNC:):

ENSG00000225233 links:

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

RPS6KC1 links:

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new If you want to explore the variant's impact on the transcript ENST00000788945.1, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.27).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.419 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

Gene	Transcript	HGVSc	Effect	Exon Rank
ENSG00000225233	ENST00000788945.1	n.297-3502A>G	intron	N/A
ENSG00000225233	ENST00000788946.1	n.302-3502A>G	intron	N/A
ENSG00000225233	ENST00000788947.1	n.457-3502A>G	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.283

AC:

42978

AN:

151938

Hom.:

6905

Cov.:

show subpopulations

Gnomad AFR

AF:

0.424

Gnomad AMI

AF:

0.416

Gnomad AMR

AF:

0.196

Gnomad ASJ

AF:

0.259

Gnomad EAS

AF:

0.0580

Gnomad SAS

AF:

0.293

Gnomad FIN

AF:

0.161

Gnomad MID

AF:

0.396

Gnomad NFE

AF:

0.251

Gnomad OTH

AF:

0.271

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

GnomAD4 genome

AF:

0.283

AC:

43006

AN:

152056

Hom.:

6913

Cov.:

AF XY:

0.278

AC XY:

20639

AN XY:

74352

show subpopulations

African (AFR)

AF:

0.424

AC:

17579

AN:

41450

American (AMR)

AF:

0.196

AC:

2987

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.259

AC:

897

AN:

3470

East Asian (EAS)

AF:

0.0578

AC:

299

AN:

5176

South Asian (SAS)

AF:

0.294

AC:

1413

AN:

4808

European-Finnish (FIN)

AF:

0.161

AC:

1706

AN:

10582

Middle Eastern (MID)

AF:

0.388

AC:

114

AN:

294

European-Non Finnish (NFE)

AF:

0.251

AC:

17059

AN:

67978

Other (OTH)

AF:

0.272

AC:

573

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1480

2960

4441

5921

7401

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

426

852

1278

1704

2130

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.257

Hom.:

940

Bravo

AF:

0.293

Asia WGS

AF:

0.213

AC:

741

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.27

CADD

Benign

(source)

DANN

Benign

0.81

PhyloP100

0.27

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over