rs1286083

Variant names:

• chr14-90976435-T-C
• rs1286083
• NM_004755.4:c.394+1871A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 35 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004755.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPS6KA5	NM_004755.4	MANE Select	c.394+1871A>G		intron	N/A	NP_004746.2
	RPS6KA5	NM_001322229.2		c.394+1871A>G		intron	N/A	NP_001309158.1
	RPS6KA5	NM_001322236.2		c.394+1871A>G		intron	N/A	NP_001309165.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPS6KA5	ENST00000614987.5	TSL:1 MANE Select	c.394+1871A>G		intron	N/A	ENSP00000479667.1
	RPS6KA5	ENST00000418736.6	TSL:1	c.394+1871A>G		intron	N/A	ENSP00000402787.2
	RPS6KA5	ENST00000554206.1	TSL:1	n.394+1871A>G		intron	N/A	ENSP00000450591.1

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

African (AFR) AF: 0.256 AC: 10602 AN: 41440

American (AMR) AF: 0.162 AC: 2477 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.270 AC: 938 AN: 3472

East Asian (EAS) AF: 0.321 AC: 1656 AN: 5162

South Asian (SAS) AF: 0.210 AC: 1008 AN: 4808

European-Finnish (FIN) AF: 0.142 AC: 1501 AN: 10562

Middle Eastern (MID) AF: 0.265 AC: 78 AN: 294

European-Non Finnish (NFE) AF: 0.188 AC: 12750 AN: 67982

Other (OTH) AF: 0.214 AC: 452 AN: 2114

Alfa AF: 0.201 Hom.: 10359

Bravo AF: 0.213

Asia WGS AF: 0.307 AC: 1066 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.20
DANN	Benign	0.69
PhyloP100		-1.7
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1286083; hg19: chr14-91442779;