rs11144870

chr9-76389297-C-T

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	UniProt
RFK	NM_018339.6	c.235-641G>A		intron_variant		ENST00000376736.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RFK	ENST00000376736.6	c.235-641G>A		intron_variant		1	NM_018339.6	P1

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

Gnomad4 AFR AF: 0.0469

Gnomad4 AMR AF: 0.155

Gnomad4 ASJ AF: 0.227

Gnomad4 EAS AF: 0.0305

Gnomad4 SAS AF: 0.178

Gnomad4 FIN AF: 0.241

Gnomad4 NFE AF: 0.260

Gnomad4 OTH AF: 0.164

Alfa AF: 0.240 Hom.: 9876

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

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: rs11144870; hg19: chr9-79004213;