rs144204753

Variant names:

• chr22-42619728-G-C
• rs144204753
• ENST00000470741.1:n.3085C>G

Your query was ambiguous. Multiple possible variants found:

• chr22-42619728-G-C
• chr22-42619728-G-T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS1

The ENST00000470741.1(CYB5R3):​n.3085C>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000194 in 1,525,624 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: 𝑓 0.00099 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00011 (0 hom.)
• Consequence: CYB5R3 ENST00000470741.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.58
• Publications: 0 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: STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• hereditary methemoglobinemia

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000289517 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.000991 (151/152344) while in subpopulation AFR AF = 0.00351 (146/41574). AF 95% confidence interval is 0.00305. There are 0 homozygotes in GnomAd4. There are 74 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000470741.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYB5R3	NM_000398.7	MANE Select	c.*45C>G		3_prime_UTR	Exon 9 of 9	NP_000389.1
	CYB5R3	NM_001171660.2		c.*45C>G		3_prime_UTR	Exon 9 of 9	NP_001165131.1
	CYB5R3	NM_001129819.2		c.*45C>G		3_prime_UTR	Exon 9 of 9	NP_001123291.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYB5R3	ENST00000470741.1	TSL:1	n.3085C>G		non_coding_transcript_exon	Exon 6 of 6
	ENSG00000289517	ENST00000617178.5	TSL:1	n.*45C>G		non_coding_transcript_exon	Exon 4 of 14	ENSP00000482500.2
	CYB5R3	ENST00000352397.10	TSL:1 MANE Select	c.*45C>G		3_prime_UTR	Exon 9 of 9	ENSP00000338461.6

Frequencies

GnomAD3 genomes AF: 0.000992 AC: 151 AN: 152226 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00352

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000327

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000274 AC: 39 AN: 142484 AF XY: 0.000264

Gnomad AFR exome AF: 0.00410

Gnomad AMR exome AF: 0.0000410

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000240

GnomAD4 exome AF: 0.000106 AC: 145 AN: 1373280 Hom.: 0 Cov.: 31 AF XY: 0.0000799 AC XY: 54 AN XY: 675818

African (AFR) AF: 0.00406 AC: 130 AN: 32016

American (AMR) AF: 0.0000283 AC: 1 AN: 35398

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23976

East Asian (EAS) AF: 0.00 AC: 0 AN: 36486

South Asian (SAS) AF: 0.0000129 AC: 1 AN: 77268

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 36468

Middle Eastern (MID) AF: 0.000194 AC: 1 AN: 5142

European-Non Finnish (NFE) AF: 9.35e-7 AC: 1 AN: 1069172

Other (OTH) AF: 0.000192 AC: 11 AN: 57354

GnomAD4 genome AF: 0.000991 AC: 151 AN: 152344 Hom.: 0 Cov.: 33 AF XY: 0.000993 AC XY: 74 AN XY: 74494

African (AFR) AF: 0.00351 AC: 146 AN: 41574

American (AMR) AF: 0.000327 AC: 5 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10632

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68024

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.000769 Hom.: 0

Bravo AF: 0.00113

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	4.9
DANN	Benign	0.71
PhyloP100		1.6
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: rs144204753; hg19: chr22-43015734;