22-42619728-G-T

Variant names:

• chr22-42619728-G-T
• NM_000398.7:c.*45C>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_000398.7(CYB5R3):​c.*45C>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 0.000000728 in 1,373,278 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 7.3e-7 (0 hom.)
• Consequence: CYB5R3 NM_000398.7 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.58

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]

ENSG00000289517 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYB5R3	NM_000398.7	c.*45C>A		3_prime_UTR_variant	Exon 9 of 9	ENST00000352397.10	NP_000389.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYB5R3	ENST00000352397	c.*45C>A		3_prime_UTR_variant	Exon 9 of 9	1	NM_000398.7	ENSP00000338461.6
ENSG00000289517	ENST00000617178.5	n.*45C>A		non_coding_transcript_exon_variant	Exon 4 of 14	1		ENSP00000482500.2
ENSG00000289517	ENST00000617178.5	n.*45C>A		3_prime_UTR_variant	Exon 4 of 14	1		ENSP00000482500.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.28e-7 AC: 1 AN: 1373278 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 675816

Gnomad4 AFR exome AF: 0.00

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: 0.00

Gnomad4 OTH exome AF: 0.0000174

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	4.9
DANN	Benign	0.82
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

No publications associated with this variant yet.

Other links and lift over

hg19: chr22-43015734;