rs137123

chr22-42619486-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000398.7(CYB5R3):c.*287C>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 0.258 in 481,864 control chromosomes in the GnomAD database, including 24,620 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.34 (13022 hom., cov: 33)
  • Exomes 𝑓: 0.22 (11598 hom.)
• Consequence: CYB5R3 NM_000398.7 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.70

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP6: Variant 22-42619486-G-T is Benign according to our data. Variant chr22-42619486-G-T is described in ClinVar as [Benign]. Clinvar id is 1271243.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.681 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CYB5R3	NM_000398.7	c.*287C>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.*287C>A		3_prime_UTR_variant	9/9	1	NM_000398.7	P3

Frequencies

GnomAD3 genomes AF: 0.339 AC: 51417 AN: 151850 Hom.: 13002 Cov.: 33

Gnomad AFR AF: 0.688

Gnomad AMI AF: 0.136

Gnomad AMR AF: 0.219

Gnomad ASJ AF: 0.158

Gnomad EAS AF: 0.686

Gnomad SAS AF: 0.273

Gnomad FIN AF: 0.171

Gnomad MID AF: 0.291

Gnomad NFE AF: 0.171

Gnomad OTH AF: 0.301

GnomAD4 exome AF: 0.221 AC: 72790 AN: 329896 Hom.: 11598 Cov.: 0 AF XY: 0.220 AC XY: 37997 AN XY: 172384

Gnomad4 AFR exome AF: 0.678

Gnomad4 AMR exome AF: 0.178

Gnomad4 ASJ exome AF: 0.139

Gnomad4 EAS exome AF: 0.640

Gnomad4 SAS exome AF: 0.236

Gnomad4 FIN exome AF: 0.171

Gnomad4 NFE exome AF: 0.163

Gnomad4 OTH exome AF: 0.236

GnomAD4 genome AF: 0.339 AC: 51491 AN: 151968 Hom.: 13022 Cov.: 33 AF XY: 0.336 AC XY: 24964 AN XY: 74302

Gnomad4 AFR AF: 0.688

Gnomad4 AMR AF: 0.219

Gnomad4 ASJ AF: 0.158

Gnomad4 EAS AF: 0.686

Gnomad4 SAS AF: 0.273

Gnomad4 FIN AF: 0.171

Gnomad4 NFE AF: 0.171

Gnomad4 OTH AF: 0.299

Alfa AF: 0.262 Hom.: 1000

Bravo AF: 0.360

Asia WGS AF: 0.438 AC: 1519 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	0.043
Dann	Benign	0.59
RBP_binding_hub_radar		1.0
RBP_regulation_power_radar		2.1

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: rs137123; hg19: chr22-43015492; COSMIC: COSV52810176; COSMIC: COSV52810176;