rs7284807

chr22-42619381-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000398.7(CYB5R3):c.*392G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0283 in 223,928 control chromosomes in the GnomAD database, including 409 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 0.039 (380 hom., cov: 33)
  • Exomes 𝑓: 0.0058 (29 hom.)
• Consequence: CYB5R3 NM_000398.7 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.76

Genes affected

CYB5R3 (HGNC:2873): (cytochrome b5 reductase 3) This gene encodes cytochrome b5 reductase, which includes a membrane-bound form in somatic cells (anchored in the endoplasmic reticulum, mitochondrial and other membranes) and a soluble form in erythrocytes. The membrane-bound form exists mainly on the cytoplasmic side of the endoplasmic reticulum and functions in desaturation and elongation of fatty acids, in cholesterol biosynthesis, and in drug metabolism. The erythrocyte form is located in a soluble fraction of circulating erythrocytes and is involved in methemoglobin reduction. The membrane-bound form has both membrane-binding and catalytic domains, while the soluble form has only the catalytic domain. Alternate splicing results in multiple transcript variants. Mutations in this gene cause methemoglobinemias. [provided by RefSeq, Jan 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.133 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CYB5R3	NM_000398.7	c.*392G>C		3_prime_UTR_variant	9/9	ENST00000352397.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYB5R3	ENST00000352397.10	c.*392G>C		3_prime_UTR_variant	9/9	1	NM_000398.7	P3

Frequencies

GnomAD3 genomes AF: 0.0389 AC: 5916 AN: 152226 Hom.: 380 Cov.: 33

Gnomad AFR AF: 0.136

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0139

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000827

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000220

Gnomad OTH AF: 0.0211

GnomAD4 exome AF: 0.00576 AC: 412 AN: 71584 Hom.: 29 Cov.: 0 AF XY: 0.00487 AC XY: 183 AN XY: 37540

Gnomad4 AFR exome AF: 0.120

Gnomad4 AMR exome AF: 0.00560

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000591

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000234

Gnomad4 OTH exome AF: 0.00804

GnomAD4 genome AF: 0.0389 AC: 5928 AN: 152344 Hom.: 380 Cov.: 33 AF XY: 0.0372 AC XY: 2773 AN XY: 74498

Gnomad4 AFR AF: 0.136

Gnomad4 AMR AF: 0.0139

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000621

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000220

Gnomad4 OTH AF: 0.0208

Alfa AF: 0.0295 Hom.: 26

Bravo AF: 0.0446

Asia WGS AF: 0.0110 AC: 37 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	1.0
Dann	Benign	0.55
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs7284807; hg19: chr22-43015387;