2-27834956-T-C

Variant names:

• chr2-27834956-T-C
• rs4666022
• NM_022128.3:c.515-2179A>G

Variant summary

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

The NM_022128.3(RBKS):​c.515-2179A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.343 in 151,938 control chromosomes in the GnomAD database, including 10,777 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 0.34 (10777 hom., cov: 32)
• Consequence: RBKS NM_022128.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.663
• Publications: 5 publications found

Genes affected

RBKS (HGNC:30325): (ribokinase) This gene encodes a member of the carbohydrate kinase PfkB family. The encoded protein phosphorylates ribose to form ribose-5-phosphate in the presence of ATP and magnesium as a first step in ribose metabolism. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2013]

MRPL33 (HGNC:14487): (mitochondrial ribosomal protein L33) Mammalian mitochondrial ribosomal proteins are encoded by nuclear genes and help in protein synthesis within the mitochondrion. Mitochondrial ribosomes (mitoribosomes) consist of a small 28S subunit and a large 39S subunit. They have an estimated 75% protein to rRNA composition compared to prokaryotic ribosomes, where this ratio is reversed. Another difference between mammalian mitoribosomes and prokaryotic ribosomes is that the latter contain a 5S rRNA. Among different species, the proteins comprising the mitoribosome differ greatly in sequence, and sometimes in biochemical properties, which prevents easy recognition by sequence homology. This gene encodes a 39S subunit protein. Alternatively spliced transcript variants encoding different isoforms have been described. [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 (EAS) allele frequency at 95% confidence interval = 0.611 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RBKS	NM_022128.3	c.515-2179A>G		intron_variant	Intron 5 of 7	ENST00000302188.8	NP_071411.1
RBKS	NM_001287580.2	c.314-2179A>G		intron_variant	Intron 6 of 8		NP_001274509.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RBKS	ENST00000302188.8	c.515-2179A>G		intron_variant	Intron 5 of 7	1	NM_022128.3	ENSP00000306817.3
RBKS	ENST00000449378.1	n.*1442-2179A>G		intron_variant	Intron 6 of 8	1		ENSP00000413789.1
RBKS	ENST00000458185.1	c.95-2179A>G		intron_variant	Intron 1 of 3	3		ENSP00000393558.1
MRPL33	ENST00000448427.1	n.164+52262T>C		intron_variant	Intron 3 of 5	4		ENSP00000407385.1

Frequencies

GnomAD3 genomes AF: 0.342 AC: 51989 AN: 151820 Hom.: 10734 Cov.: 32

Gnomad AFR AF: 0.532

Gnomad AMI AF: 0.287

Gnomad AMR AF: 0.409

Gnomad ASJ AF: 0.251

Gnomad EAS AF: 0.629

Gnomad SAS AF: 0.296

Gnomad FIN AF: 0.285

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.210

Gnomad OTH AF: 0.309

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

GnomAD4 genome AF: 0.343 AC: 52098 AN: 151938 Hom.: 10777 Cov.: 32 AF XY: 0.350 AC XY: 26019 AN XY: 74272

African (AFR) AF: 0.533 AC: 22082 AN: 41408

American (AMR) AF: 0.409 AC: 6246 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.251 AC: 872 AN: 3472

East Asian (EAS) AF: 0.630 AC: 3252 AN: 5166

South Asian (SAS) AF: 0.296 AC: 1424 AN: 4814

European-Finnish (FIN) AF: 0.285 AC: 3008 AN: 10550

Middle Eastern (MID) AF: 0.190 AC: 56 AN: 294

European-Non Finnish (NFE) AF: 0.210 AC: 14250 AN: 67954

Other (OTH) AF: 0.307 AC: 646 AN: 2102

Alfa AF: 0.257 Hom.: 1969

Bravo AF: 0.366

Asia WGS AF: 0.478 AC: 1662 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	0.57
DANN	Benign	0.71
PhyloP100		-0.66
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: rs4666022; hg19: chr2-28057823;