chr1-26539014-C-T

Position:

• chr1-26539014-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.108+2045C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.119 in 152,226 control chromosomes in the GnomAD database, including 1,296 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 0.12 (1296 hom., cov: 33)
• Consequence: RPS6KA1 NM_002953.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0130

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=-0.79).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.154 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RPS6KA1	NM_002953.4	c.108+2045C>T		intron_variant		ENST00000374168.7	NP_002944.2
RPS6KA1	XM_024448871.2	c.-169+2045C>T		intron_variant			XP_024304639.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPS6KA1	ENST00000374168.7	c.108+2045C>T		intron_variant		1	NM_002953.4	ENSP00000363283	P1

Frequencies

GnomAD3 genomes AF: 0.119 AC: 18140 AN: 152108 Hom.: 1291 Cov.: 33

Gnomad AFR AF: 0.0758

Gnomad AMI AF: 0.181

Gnomad AMR AF: 0.0776

Gnomad ASJ AF: 0.124

Gnomad EAS AF: 0.0146

Gnomad SAS AF: 0.0759

Gnomad FIN AF: 0.171

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.157

Gnomad OTH AF: 0.124

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

GnomAD4 genome AF: 0.119 AC: 18167 AN: 152226 Hom.: 1296 Cov.: 33 AF XY: 0.119 AC XY: 8839 AN XY: 74418

Gnomad4 AFR AF: 0.0762

Gnomad4 AMR AF: 0.0776

Gnomad4 ASJ AF: 0.124

Gnomad4 EAS AF: 0.0147

Gnomad4 SAS AF: 0.0758

Gnomad4 FIN AF: 0.171

Gnomad4 NFE AF: 0.157

Gnomad4 OTH AF: 0.124

Alfa AF: 0.138 Hom.: 556

Bravo AF: 0.109

Asia WGS AF: 0.0580 AC: 202 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	2.9
DANN	Benign	0.67

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: rs12025634; hg19: chr1-26865505;