rs79192059

chr22-42619060-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_000398.7(CYB5R3):c.*713G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00776 in 152,914 control chromosomes in the GnomAD database, including 5 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 0.0078 (5 hom., cov: 33)
  • Exomes 𝑓: 0.0037 (0 hom.)
• Consequence: CYB5R3 NM_000398.7 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.68

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=-0.71).
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00778 (1185/152370) while in subpopulation SAS AF= 0.0159 (77/4832). AF 95% confidence interval is 0.0131. There are 5 homozygotes in gnomad4. There are 547 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CYB5R3	NM_000398.7	c.*713G>A		3_prime_UTR_variant	9/9	ENST00000352397.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYB5R3	ENST00000352397.10	c.*713G>A		3_prime_UTR_variant	9/9	1	NM_000398.7	P3

Frequencies

GnomAD3 genomes AF: 0.00777 AC: 1183 AN: 152252 Hom.: 5 Cov.: 33

Gnomad AFR AF: 0.00178

Gnomad AMI AF: 0.0219

Gnomad AMR AF: 0.00844

Gnomad ASJ AF: 0.0207

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0157

Gnomad FIN AF: 0.00405

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0110

Gnomad OTH AF: 0.00764

GnomAD4 exome AF: 0.00368 AC: 2 AN: 544 Hom.: 0 Cov.: 0 AF XY: 0.00340 AC XY: 1 AN XY: 294

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00459

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.00778 AC: 1185 AN: 152370 Hom.: 5 Cov.: 33 AF XY: 0.00734 AC XY: 547 AN XY: 74514

Gnomad4 AFR AF: 0.00178

Gnomad4 AMR AF: 0.00843

Gnomad4 ASJ AF: 0.0207

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0159

Gnomad4 FIN AF: 0.00405

Gnomad4 NFE AF: 0.0110

Gnomad4 OTH AF: 0.00756

Alfa AF: 0.00974 Hom.: 0

Bravo AF: 0.00800

Asia WGS AF: 0.00693 AC: 24 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
Cadd	Benign	3.4
Dann	Benign	0.79
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: rs79192059; hg19: chr22-43015066;