rs79192059

Variant names:

• chr22-42619060-C-T
• rs79192059
• NM_000398.7:c.*713G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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]

CYB5R3 Gene-Disease associations (from GenCC):

• methemoglobinemia

  Inheritance: AR Classification: DEFINITIVE Submitted by: Illumina
• methemoglobinemia due to deficiency of methemoglobin reductase

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, ClinGen, Labcorp Genetics (formerly Invitae)
• hereditary methemoglobinemia

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000289517 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 5 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000398.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYB5R3	NM_000398.7	MANE Select	c.*713G>A		3_prime_UTR	Exon 9 of 9	NP_000389.1	P00387-1
	CYB5R3	NM_001171660.2		c.*713G>A		3_prime_UTR	Exon 9 of 9	NP_001165131.1	P00387-3
	CYB5R3	NM_001129819.2		c.*713G>A		3_prime_UTR	Exon 9 of 9	NP_001123291.1	P00387-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYB5R3	ENST00000352397.10	TSL:1 MANE Select	c.*713G>A		3_prime_UTR	Exon 9 of 9	ENSP00000338461.6	P00387-1
	CYB5R3	ENST00000407332.6	TSL:1	c.*713G>A		3_prime_UTR	Exon 9 of 9	ENSP00000384457.2	A0A8J8Z3C6
	CYB5R3	ENST00000470741.1	TSL:1	n.3753G>A		non_coding_transcript_exon	Exon 6 of 6

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

African (AFR) AC: 0 AN: 0

American (AMR) AF: 0.00 AC: 0 AN: 38

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2

East Asian (EAS) AF: 0.00 AC: 0 AN: 4

South Asian (SAS) AF: 0.00 AC: 0 AN: 22

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 16

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00459 AC: 2 AN: 436

Other (OTH) AF: 0.00 AC: 0 AN: 26

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

African (AFR) AF: 0.00178 AC: 74 AN: 41594

American (AMR) AF: 0.00843 AC: 129 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0207 AC: 72 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.0159 AC: 77 AN: 4832

European-Finnish (FIN) AF: 0.00405 AC: 43 AN: 10622

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.0110 AC: 749 AN: 68040

Other (OTH) AF: 0.00756 AC: 16 AN: 2116

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	3.4
DANN	Benign	0.79
PhyloP100		-1.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs79192059; hg19: chr22-43015066;