rs144204753

chr22-42619728-G-C

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 2P and 8B. PM2 BP4_Strong BS1

The NM_000398.7(CYB5R3):c.*45C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000194 in 1,525,624 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.00099 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00011 (0 hom.)
• Consequence: CYB5R3 NM_000398.7 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.58

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 Likely_benign. Variant got -6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000991 (151/152344) while in subpopulation AFR AF= 0.00351 (146/41574). AF 95% confidence interval is 0.00305. There are 0 homozygotes in gnomad4. There are 74 alleles in male gnomad4 subpopulation. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CYB5R3	NM_000398.7	c.*45C>G		3_prime_UTR_variant	9/9	ENST00000352397.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYB5R3	ENST00000352397.10	c.*45C>G		3_prime_UTR_variant	9/9	1	NM_000398.7	P3

Frequencies

GnomAD3 genomes AF: 0.000992 AC: 151 AN: 152226 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00352

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000327

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000274 AC: 39 AN: 142484 Hom.: 0 AF XY: 0.000264 AC XY: 20 AN XY: 75642

Gnomad AFR exome AF: 0.00410

Gnomad AMR exome AF: 0.0000410

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000481

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000240

GnomAD4 exome AF: 0.000106 AC: 145 AN: 1373280 Hom.: 0 Cov.: 31 AF XY: 0.0000799 AC XY: 54 AN XY: 675818

Gnomad4 AFR exome AF: 0.00406

Gnomad4 AMR exome AF: 0.0000283

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000129

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.35e-7

Gnomad4 OTH exome AF: 0.000192

GnomAD4 genome AF: 0.000991 AC: 151 AN: 152344 Hom.: 0 Cov.: 33 AF XY: 0.000993 AC XY: 74 AN XY: 74494

Gnomad4 AFR AF: 0.00351

Gnomad4 AMR AF: 0.000327

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000769 Hom.: 0

Bravo AF: 0.00113

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	4.9
Dann	Benign	0.71

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: rs144204753; hg19: chr22-43015734;