rs4666014

Variant names:

• chr2-27796308-G-A
• rs4666014
• NM_022128.3:c.796-14520C>T

Your query was ambiguous. Multiple possible variants found:

• chr2-27796308-G-A
• chr2-27796308-G-C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_022128.3(RBKS):​c.796-14520C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.357 in 151,938 control chromosomes in the GnomAD database, including 12,001 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 0.36 (12001 hom., cov: 32)
• Consequence: RBKS NM_022128.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.42
• Publications: 16 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.4).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.585 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RBKS	NM_022128.3	c.796-14520C>T		intron_variant	Intron 7 of 7	ENST00000302188.8	NP_071411.1
RBKS	NM_001287580.2	c.595-14520C>T		intron_variant	Intron 8 of 8		NP_001274509.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RBKS	ENST00000302188.8	c.796-14520C>T		intron_variant	Intron 7 of 7	1	NM_022128.3	ENSP00000306817.3
RBKS	ENST00000449378.1	n.*1723-14520C>T		intron_variant	Intron 8 of 8	1		ENSP00000413789.1
MRPL33	ENST00000448427.1	n.164+13614G>A		intron_variant	Intron 3 of 5	4		ENSP00000407385.1

Frequencies

GnomAD3 genomes AF: 0.357 AC: 54156 AN: 151820 Hom.: 11961 Cov.: 32

Gnomad AFR AF: 0.591

Gnomad AMI AF: 0.275

Gnomad AMR AF: 0.413

Gnomad ASJ AF: 0.244

Gnomad EAS AF: 0.590

Gnomad SAS AF: 0.315

Gnomad FIN AF: 0.286

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.207

Gnomad OTH AF: 0.312

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

GnomAD4 genome AF: 0.357 AC: 54263 AN: 151938 Hom.: 12001 Cov.: 32 AF XY: 0.364 AC XY: 27064 AN XY: 74264

African (AFR) AF: 0.592 AC: 24495 AN: 41398

American (AMR) AF: 0.413 AC: 6310 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.244 AC: 844 AN: 3464

East Asian (EAS) AF: 0.590 AC: 3050 AN: 5168

South Asian (SAS) AF: 0.315 AC: 1517 AN: 4818

European-Finnish (FIN) AF: 0.286 AC: 3009 AN: 10534

Middle Eastern (MID) AF: 0.187 AC: 55 AN: 294

European-Non Finnish (NFE) AF: 0.207 AC: 14079 AN: 67968

Other (OTH) AF: 0.310 AC: 654 AN: 2110

Alfa AF: 0.255 Hom.: 10183

Bravo AF: 0.382

Asia WGS AF: 0.481 AC: 1669 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.40
CADD	Benign	18
DANN	Benign	0.76
PhyloP100		1.4
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: rs4666014; hg19: chr2-28019175;