rs137117

Variant names:

• chr22-42616847-A-C
• rs137117
• ENST00000617178.5:n.*207-726T>G

Your query was ambiguous. Multiple possible variants found:

• chr22-42616847-A-C
• chr22-42616847-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000617178.5(ENSG00000289517):​n.*207-726T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.501 in 151,716 control chromosomes in the GnomAD database, including 22,972 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 0.50 (22972 hom., cov: 29)
• Consequence: ENSG00000289517 ENST00000617178.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.05
• Publications: 4 publications found

Genes affected

ENSG00000289517 (HGNC:):

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.837 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000289517	ENST00000617178.5	n.*207-726T>G		intron_variant	Intron 4 of 13	1		ENSP00000482500.2
CYB5R3	ENST00000693367.1	c.843-729T>G		intron_variant	Intron 9 of 9			ENSP00000508815.1
ENSG00000270022	ENST00000729791.1	n.212+1392A>C		intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes AF: 0.501 AC: 75888 AN: 151598 Hom.: 22920 Cov.: 29

Gnomad AFR AF: 0.844

Gnomad AMI AF: 0.171

Gnomad AMR AF: 0.425

Gnomad ASJ AF: 0.287

Gnomad EAS AF: 0.767

Gnomad SAS AF: 0.442

Gnomad FIN AF: 0.351

Gnomad MID AF: 0.437

Gnomad NFE AF: 0.333

Gnomad OTH AF: 0.454

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.501 AC: 75993 AN: 151716 Hom.: 22972 Cov.: 29 AF XY: 0.499 AC XY: 37018 AN XY: 74136

African (AFR) AF: 0.844 AC: 34986 AN: 41440

American (AMR) AF: 0.425 AC: 6469 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.287 AC: 995 AN: 3470

East Asian (EAS) AF: 0.766 AC: 3906 AN: 5096

South Asian (SAS) AF: 0.441 AC: 2116 AN: 4802

European-Finnish (FIN) AF: 0.351 AC: 3690 AN: 10508

Middle Eastern (MID) AF: 0.442 AC: 130 AN: 294

European-Non Finnish (NFE) AF: 0.333 AC: 22594 AN: 67854

Other (OTH) AF: 0.452 AC: 951 AN: 2104

Alfa AF: 0.423 Hom.: 2108

Bravo AF: 0.522

Asia WGS AF: 0.573 AC: 1994 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.1
DANN	Benign	0.15
PhyloP100		-2.1

Splicing

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

Other links and lift over

dbSNP: rs137117; hg19: chr22-43012853;