rs139442000

Positions:

• chr22-42619582-G-A

Variant summary

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

The NM_000398.7(CYB5R3):​c.*191C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00233 in 610,098 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 0.0017 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0025 (5 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=-0.82).
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00173 (263/152344) while in subpopulation SAS AF= 0.00455 (22/4832). AF 95% confidence interval is 0.00308. There are 0 homozygotes in gnomad4. There are 115 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAdExome4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CYB5R3	NM_000398.7	c.*191C>T		3_prime_UTR_variant	9/9	ENST00000352397.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYB5R3	ENST00000352397.10	c.*191C>T		3_prime_UTR_variant	9/9	1	NM_000398.7	P3

Frequencies

GnomAD3 genomes AF: 0.00173 AC: 263 AN: 152226 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000410

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00144

Gnomad ASJ AF: 0.00432

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00455

Gnomad FIN AF: 0.000471

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00259

Gnomad OTH AF: 0.00239

GnomAD4 exome AF: 0.00253 AC: 1158 AN: 457754 Hom.: 5 Cov.: 5 AF XY: 0.00266 AC XY: 640 AN XY: 240748

Gnomad4 AFR exome AF: 0.000796

Gnomad4 AMR exome AF: 0.00104

Gnomad4 ASJ exome AF: 0.00496

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00461

Gnomad4 FIN exome AF: 0.000507

Gnomad4 NFE exome AF: 0.00274

Gnomad4 OTH exome AF: 0.00252

GnomAD4 genome AF: 0.00173 AC: 263 AN: 152344 Hom.: 0 Cov.: 33 AF XY: 0.00154 AC XY: 115 AN XY: 74498

Gnomad4 AFR AF: 0.000409

Gnomad4 AMR AF: 0.00144

Gnomad4 ASJ AF: 0.00432

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00455

Gnomad4 FIN AF: 0.000471

Gnomad4 NFE AF: 0.00259

Gnomad4 OTH AF: 0.00237

Alfa AF: 0.00228 Hom.: 0

Bravo AF: 0.00170

Asia WGS AF: 0.00173 AC: 6 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	6.1
DANN	Benign	0.66
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: rs139442000; hg19: chr22-43015588;