chr14-90928787-G-T

Variant names:

• chr14-90928787-G-T
• rs1286124
• NM_004755.4:c.619-5591C>A

Variant summary

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

The NM_004755.4(RPS6KA5):​c.619-5591C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.642 in 149,734 control chromosomes in the GnomAD database, including 32,126 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 0.64 (32126 hom., cov: 29)
• Consequence: RPS6KA5 NM_004755.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.59

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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.856 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPS6KA5	NM_004755.4	c.619-5591C>A		intron_variant	Intron 5 of 16	ENST00000614987.5	NP_004746.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPS6KA5	ENST00000614987.5	c.619-5591C>A		intron_variant	Intron 5 of 16	1	NM_004755.4	ENSP00000479667.1

Frequencies

GnomAD3 genomes AF: 0.642 AC: 96016 AN: 149658 Hom.: 32109 Cov.: 29

Gnomad AFR AF: 0.430

Gnomad AMI AF: 0.586

Gnomad AMR AF: 0.687

Gnomad ASJ AF: 0.677

Gnomad EAS AF: 0.877

Gnomad SAS AF: 0.635

Gnomad FIN AF: 0.761

Gnomad MID AF: 0.616

Gnomad NFE AF: 0.723

Gnomad OTH AF: 0.645

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

GnomAD4 genome AF: 0.642 AC: 96059 AN: 149734 Hom.: 32126 Cov.: 29 AF XY: 0.645 AC XY: 47130 AN XY: 73060

Gnomad4 AFR AF: 0.430

Gnomad4 AMR AF: 0.688

Gnomad4 ASJ AF: 0.677

Gnomad4 EAS AF: 0.877

Gnomad4 SAS AF: 0.636

Gnomad4 FIN AF: 0.761

Gnomad4 NFE AF: 0.723

Gnomad4 OTH AF: 0.648

Alfa AF: 0.597 Hom.: 2472

Bravo AF: 0.628

Asia WGS AF: 0.757 AC: 2604 AN: 3440

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	3.9
DANN	Benign	0.19

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: rs1286124; hg19: chr14-91395131;