rs1286083

Positions:

• chr14-90976435-T-C

Variant summary

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

The NM_004755.4(RPS6KA5):​c.394+1871A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.208 in 152,022 control chromosomes in the GnomAD database, including 3,494 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 0.21 (3494 hom., cov: 31)
• Consequence: RPS6KA5 NM_004755.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.73

Genes affected

RPS6KA5 (HGNC:10434): (ribosomal protein S6 kinase A5) Enables ATP binding activity and protein serine/threonine kinase activity. Involved in several processes, including histone-serine phosphorylation; positive regulation of histone modification; and regulation of transcription, DNA-templated. Located in cytoplasm and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.308 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RPS6KA5	NM_004755.4	c.394+1871A>G		intron_variant		ENST00000614987.5	NP_004746.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPS6KA5	ENST00000614987.5	c.394+1871A>G		intron_variant		1	NM_004755.4	ENSP00000479667	P1

Frequencies

GnomAD3 genomes AF: 0.208 AC: 31526 AN: 151904 Hom.: 3482 Cov.: 31

Gnomad AFR AF: 0.256

Gnomad AMI AF: 0.131

Gnomad AMR AF: 0.162

Gnomad ASJ AF: 0.270

Gnomad EAS AF: 0.320

Gnomad SAS AF: 0.208

Gnomad FIN AF: 0.142

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.188

Gnomad OTH AF: 0.211

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

GnomAD4 genome AF: 0.208 AC: 31581 AN: 152022 Hom.: 3494 Cov.: 31 AF XY: 0.205 AC XY: 15264 AN XY: 74308

Gnomad4 AFR AF: 0.256

Gnomad4 AMR AF: 0.162

Gnomad4 ASJ AF: 0.270

Gnomad4 EAS AF: 0.321

Gnomad4 SAS AF: 0.210

Gnomad4 FIN AF: 0.142

Gnomad4 NFE AF: 0.188

Gnomad4 OTH AF: 0.214

Alfa AF: 0.200 Hom.: 3402

Bravo AF: 0.213

Asia WGS AF: 0.307 AC: 1066 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.20
DANN	Benign	0.69

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1286083; hg19: chr14-91442779;