rs2278978

Variant names:

• chr1-26546754-A-G
• rs2278978
• NM_002953.4:c.109-113A>G

Variant summary

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

The NM_002953.4(RPS6KA1):​c.109-113A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.737 in 749,456 control chromosomes in the GnomAD database, including 205,097 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 0.77 (45634 hom., cov: 32)
  • Exomes 𝑓: 0.73 (159463 hom.)
• Consequence: RPS6KA1 NM_002953.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.334
• Publications: 14 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.883 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPS6KA1	NM_002953.4	c.109-113A>G		intron_variant	Intron 2 of 21	ENST00000374168.7	NP_002944.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPS6KA1	ENST00000374168.7	c.109-113A>G		intron_variant	Intron 2 of 21	1	NM_002953.4	ENSP00000363283.2

Frequencies

GnomAD3 genomes AF: 0.770 AC: 117071 AN: 152044 Hom.: 45598 Cov.: 32

Gnomad AFR AF: 0.890

Gnomad AMI AF: 0.719

Gnomad AMR AF: 0.685

Gnomad ASJ AF: 0.639

Gnomad EAS AF: 0.784

Gnomad SAS AF: 0.683

Gnomad FIN AF: 0.754

Gnomad MID AF: 0.788

Gnomad NFE AF: 0.731

Gnomad OTH AF: 0.763

GnomAD4 exome AF: 0.729 AC: 435237 AN: 597294 Hom.: 159463 AF XY: 0.723 AC XY: 228721 AN XY: 316336

African (AFR) AF: 0.891 AC: 14572 AN: 16352

American (AMR) AF: 0.666 AC: 20350 AN: 30558

Ashkenazi Jewish (ASJ) AF: 0.664 AC: 11627 AN: 17500

East Asian (EAS) AF: 0.769 AC: 24695 AN: 32096

South Asian (SAS) AF: 0.662 AC: 39268 AN: 59290

European-Finnish (FIN) AF: 0.751 AC: 29001 AN: 38598

Middle Eastern (MID) AF: 0.709 AC: 2532 AN: 3570

European-Non Finnish (NFE) AF: 0.734 AC: 270201 AN: 368090

Other (OTH) AF: 0.736 AC: 22991 AN: 31240

GnomAD4 genome AF: 0.770 AC: 117162 AN: 152162 Hom.: 45634 Cov.: 32 AF XY: 0.766 AC XY: 56931 AN XY: 74368

African (AFR) AF: 0.890 AC: 36979 AN: 41532

American (AMR) AF: 0.685 AC: 10465 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.639 AC: 2216 AN: 3470

East Asian (EAS) AF: 0.784 AC: 4050 AN: 5166

South Asian (SAS) AF: 0.682 AC: 3290 AN: 4826

European-Finnish (FIN) AF: 0.754 AC: 7993 AN: 10600

Middle Eastern (MID) AF: 0.793 AC: 233 AN: 294

European-Non Finnish (NFE) AF: 0.731 AC: 49677 AN: 67972

Other (OTH) AF: 0.761 AC: 1606 AN: 2110

Alfa AF: 0.743 Hom.: 143149

Bravo AF: 0.773

Asia WGS AF: 0.741 AC: 2576 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.4
DANN	Benign	0.34
PhyloP100		0.33
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: rs2278978; hg19: chr1-26873245; COSMIC: COSV64809871; COSMIC: COSV64809871;