rs190737

chr1-26572953-C-Achr1-26572953-C-Gchr1-26572953-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002953.4(RPS6KA1):c.1948-271C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.554 in 152,080 control chromosomes in the GnomAD database, including 24,321 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 0.55 (24321 hom., cov: 32)
• Consequence: RPS6KA1 NM_002953.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0110

Genes affected

RPS6KA1 (HGNC:10430): (ribosomal protein S6 kinase A1) This gene encodes a member of the RSK (ribosomal S6 kinase) family of serine/threonine kinases. This kinase contains 2 nonidentical kinase catalytic domains and phosphorylates various substrates, including members of the mitogen-activated kinase (MAPK) signalling pathway. The activity of this protein has been implicated in controlling cell growth and differentiation. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.956 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RPS6KA1	NM_002953.4	c.1948-271C>A		intron_variant		ENST00000374168.7
RPS6KA1	NM_001006665.2	c.1975-271C>A		intron_variant
RPS6KA1	NM_001330441.2	c.1900-271C>A		intron_variant
RPS6KA1	XM_024448871.2	c.1672-271C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RPS6KA1	ENST00000374168.7	c.1948-271C>A		intron_variant		1	NM_002953.4	P1

Frequencies

GnomAD3 genomes AF: 0.554 AC: 84198 AN: 151962 Hom.: 24316 Cov.: 32

Gnomad AFR AF: 0.477

Gnomad AMI AF: 0.645

Gnomad AMR AF: 0.667

Gnomad ASJ AF: 0.643

Gnomad EAS AF: 0.979

Gnomad SAS AF: 0.828

Gnomad FIN AF: 0.526

Gnomad MID AF: 0.551

Gnomad NFE AF: 0.522

Gnomad OTH AF: 0.568

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

GnomAD4 genome AF: 0.554 AC: 84238 AN: 152080 Hom.: 24321 Cov.: 32 AF XY: 0.565 AC XY: 42022 AN XY: 74330

Gnomad4 AFR AF: 0.477

Gnomad4 AMR AF: 0.667

Gnomad4 ASJ AF: 0.643

Gnomad4 EAS AF: 0.979

Gnomad4 SAS AF: 0.826

Gnomad4 FIN AF: 0.526

Gnomad4 NFE AF: 0.522

Gnomad4 OTH AF: 0.572

Alfa AF: 0.542 Hom.: 27705

Bravo AF: 0.559

Asia WGS AF: 0.863 AC: 3002 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	5.4
Dann	Benign	0.69

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs190737; hg19: chr1-26899444;