1-26572634-C-T

Variant names:

• chr1-26572634-C-T
• rs282177
• NM_002953.4:c.1947+341C>T

Variant summary

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

The NM_002953.4(RPS6KA1):​c.1947+341C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.37 in 151,916 control chromosomes in the GnomAD database, including 11,638 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 0.37 (11638 hom., cov: 32)
• Consequence: RPS6KA1 NM_002953.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.61
• Publications: 11 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.747 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPS6KA1	NM_002953.4	c.1947+341C>T		intron_variant	Intron 20 of 21	ENST00000374168.7	NP_002944.2
RPS6KA1	NM_001006665.2	c.1974+341C>T		intron_variant	Intron 19 of 20		NP_001006666.1
RPS6KA1	NM_001330441.2	c.1899+341C>T		intron_variant	Intron 19 of 20		NP_001317370.1
RPS6KA1	XM_024448871.2	c.1671+341C>T		intron_variant	Intron 20 of 21		XP_024304639.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPS6KA1	ENST00000374168.7	c.1947+341C>T		intron_variant	Intron 20 of 21	1	NM_002953.4	ENSP00000363283.2

Frequencies

GnomAD3 genomes AF: 0.370 AC: 56100 AN: 151794 Hom.: 11626 Cov.: 32

Gnomad AFR AF: 0.492

Gnomad AMI AF: 0.346

Gnomad AMR AF: 0.397

Gnomad ASJ AF: 0.295

Gnomad EAS AF: 0.768

Gnomad SAS AF: 0.569

Gnomad FIN AF: 0.280

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.263

Gnomad OTH AF: 0.370

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

GnomAD4 genome AF: 0.370 AC: 56153 AN: 151916 Hom.: 11638 Cov.: 32 AF XY: 0.376 AC XY: 27915 AN XY: 74214

African (AFR) AF: 0.492 AC: 20362 AN: 41408

American (AMR) AF: 0.397 AC: 6052 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.295 AC: 1023 AN: 3470

East Asian (EAS) AF: 0.767 AC: 3948 AN: 5146

South Asian (SAS) AF: 0.567 AC: 2735 AN: 4820

European-Finnish (FIN) AF: 0.280 AC: 2944 AN: 10530

Middle Eastern (MID) AF: 0.310 AC: 91 AN: 294

European-Non Finnish (NFE) AF: 0.263 AC: 17890 AN: 67976

Other (OTH) AF: 0.375 AC: 792 AN: 2114

Alfa AF: 0.296 Hom.: 9319

Bravo AF: 0.382

Asia WGS AF: 0.639 AC: 2221 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.29
DANN	Benign	0.48
PhyloP100		-1.6
PromoterAI		-0.015	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs282177; hg19: chr1-26899125;