rs11144870

Variant names:

• chr9-76389297-C-T
• rs11144870
• NM_018339.6:c.235-641G>A

Variant summary

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

The NM_018339.6(RFK):​c.235-641G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.177 in 152,126 control chromosomes in the GnomAD database, including 3,122 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 0.18 (3122 hom., cov: 32)
• Consequence: RFK NM_018339.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.438
• Publications: 15 publications found

Genes affected

RFK (HGNC:30324): (riboflavin kinase) Riboflavin kinase (RFK; EC 2.7.1.26) is an essential enzyme that catalyzes the phosphorylation of riboflavin (vitamin B2) to form flavin mononucleotide (FMN), an obligatory step in vitamin B2 utilization and flavin cofactor synthesis (Karthikeyan et al., 2003 [PubMed 12623014]).[supplied by OMIM, Nov 2009]

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 (NFE) allele frequency at 95% confidence interval = 0.257 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RFK	NM_018339.6	c.235-641G>A		intron_variant	Intron 2 of 3	ENST00000376736.6	NP_060809.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RFK	ENST00000376736.6	c.235-641G>A		intron_variant	Intron 2 of 3	1	NM_018339.6	ENSP00000365926.1

Frequencies

GnomAD3 genomes AF: 0.178 AC: 26984 AN: 152008 Hom.: 3122 Cov.: 32

Gnomad AFR AF: 0.0471

Gnomad AMI AF: 0.231

Gnomad AMR AF: 0.155

Gnomad ASJ AF: 0.227

Gnomad EAS AF: 0.0306

Gnomad SAS AF: 0.179

Gnomad FIN AF: 0.241

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.260

Gnomad OTH AF: 0.167

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

GnomAD4 genome AF: 0.177 AC: 26975 AN: 152126 Hom.: 3122 Cov.: 32 AF XY: 0.176 AC XY: 13055 AN XY: 74358

African (AFR) AF: 0.0469 AC: 1950 AN: 41536

American (AMR) AF: 0.155 AC: 2372 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.227 AC: 789 AN: 3470

East Asian (EAS) AF: 0.0305 AC: 158 AN: 5180

South Asian (SAS) AF: 0.178 AC: 859 AN: 4824

European-Finnish (FIN) AF: 0.241 AC: 2548 AN: 10552

Middle Eastern (MID) AF: 0.133 AC: 39 AN: 294

European-Non Finnish (NFE) AF: 0.260 AC: 17703 AN: 67974

Other (OTH) AF: 0.164 AC: 347 AN: 2112

Alfa AF: 0.227 Hom.: 14778

Bravo AF: 0.163

Asia WGS AF: 0.0920 AC: 318 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.2
DANN	Benign	0.75
PhyloP100		-0.44
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: rs11144870; hg19: chr9-79004213;