rs8190363

Positions:

• chr22-42649614-CG-C
• chr22-42649614-CG-CGG

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The ENST00000692152.1(CYB5R3):​c.-48-12769delC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.138 in 152,366 control chromosomes in the GnomAD database, including 2,034 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.14 (2030 hom., cov: 30)
  • Exomes 𝑓: 0.13 (4 hom.)
• Consequence: CYB5R3 ENST00000692152.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.45

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 -10 ACMG points.

• BP6: Variant 22-42649614-CG-C is Benign according to our data. Variant chr22-42649614-CG-C is described in ClinVar as [Benign]. Clinvar id is 1291543.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.562 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYB5R3	ENST00000692152.1	c.-48-12769delC		intron_variant				ENSP00000509317.1
CYB5R3	ENST00000686129.1	c.-48-12769delC		intron_variant				ENSP00000508623.1
CYB5R3	ENST00000693716.1	n.250-12769delC		intron_variant

Frequencies

GnomAD3 genomes AF: 0.138 AC: 20916 AN: 151970 Hom.: 2032 Cov.: 30

Gnomad AFR AF: 0.143

Gnomad AMI AF: 0.0989

Gnomad AMR AF: 0.111

Gnomad ASJ AF: 0.0813

Gnomad EAS AF: 0.580

Gnomad SAS AF: 0.228

Gnomad FIN AF: 0.151

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.102

Gnomad OTH AF: 0.143

GnomAD4 exome AF: 0.129 AC: 36 AN: 280 Hom.: 4 Cov.: 0 AF XY: 0.140 AC XY: 26 AN XY: 186

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0833

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.500

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.250

Gnomad4 NFE exome AF: 0.136

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.138 AC: 20933 AN: 152086 Hom.: 2030 Cov.: 30 AF XY: 0.143 AC XY: 10629 AN XY: 74328

Gnomad4 AFR AF: 0.143

Gnomad4 AMR AF: 0.111

Gnomad4 ASJ AF: 0.0813

Gnomad4 EAS AF: 0.579

Gnomad4 SAS AF: 0.228

Gnomad4 FIN AF: 0.151

Gnomad4 NFE AF: 0.102

Gnomad4 OTH AF: 0.141

Alfa AF: 0.130 Hom.: 169

Bravo AF: 0.134

Asia WGS AF: 0.345 AC: 1198 AN: 3476

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

Jun 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs8190363; hg19: chr22-43045620;