rs190737

Variant names:

• chr1-26572953-C-A
• rs190737
• NM_002953.4:c.1948-271C>A

Your query was ambiguous. Multiple possible variants found:

• chr1-26572953-C-A
• chr1-26572953-C-G
• chr1-26572953-C-T

Variant summary

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

The NM_001006665.2(RPS6KA1):​c.1975-271C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.554 in 152,080 control chromosomes in the GnomAD database, including 24,321 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 0.55 (24321 hom., cov: 32)
• Consequence: RPS6KA1 NM_001006665.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0110
• Publications: 13 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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.956 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001006665.2. 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
	RPS6KA1	NM_002953.4	MANE Select	c.1948-271C>A		intron	N/A	NP_002944.2
	RPS6KA1	NM_001006665.2		c.1975-271C>A		intron	N/A	NP_001006666.1
	RPS6KA1	NM_001330441.2		c.1900-271C>A		intron	N/A	NP_001317370.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPS6KA1	ENST00000374168.7	TSL:1 MANE Select	c.1948-271C>A		intron	N/A	ENSP00000363283.2
	RPS6KA1	ENST00000531382.5	TSL:2	c.1975-271C>A		intron	N/A	ENSP00000435412.1
	RPS6KA1	ENST00000952528.1		c.1969-271C>A		intron	N/A	ENSP00000622587.1

Frequencies

GnomAD3 genomes AF: 0.554 AC: 84198 AN: 151962 Hom.: 24316 Cov.: 32

Gnomad AFR AF: 0.477

Gnomad AMI AF: 0.645

Gnomad AMR AF: 0.667

Gnomad ASJ AF: 0.643

Gnomad EAS AF: 0.979

Gnomad SAS AF: 0.828

Gnomad FIN AF: 0.526

Gnomad MID AF: 0.551

Gnomad NFE AF: 0.522

Gnomad OTH AF: 0.568

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

GnomAD4 genome AF: 0.554 AC: 84238 AN: 152080 Hom.: 24321 Cov.: 32 AF XY: 0.565 AC XY: 42022 AN XY: 74330

African (AFR) AF: 0.477 AC: 19785 AN: 41466

American (AMR) AF: 0.667 AC: 10200 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.643 AC: 2233 AN: 3472

East Asian (EAS) AF: 0.979 AC: 5058 AN: 5168

South Asian (SAS) AF: 0.826 AC: 3986 AN: 4824

European-Finnish (FIN) AF: 0.526 AC: 5568 AN: 10576

Middle Eastern (MID) AF: 0.551 AC: 162 AN: 294

European-Non Finnish (NFE) AF: 0.522 AC: 35454 AN: 67974

Other (OTH) AF: 0.572 AC: 1206 AN: 2110

Alfa AF: 0.543 Hom.: 70230

Bravo AF: 0.559

Asia WGS AF: 0.863 AC: 3002 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.4
DANN	Benign	0.69
PhyloP100		0.011
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: rs190737; hg19: chr1-26899444;