Genetic Variant ENST00000692152.1:c.-48-12769delC (chr22-42649614-CG-C) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBA1

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

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.45

Publications

1 publications found

Variant links:

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

CYB5R3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000692152.1. 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.-300delC		upstream_gene	N/A	NP_000389.1	P00387-1

Ensembl Transcripts

Gene	Transcript	HGVSc	Effect	Exon Rank	Protein	UniProt
CYB5R3	ENST00000692152.1	c.-48-12769delC	intron	N/A	ENSP00000509317.1	P00387-2
CYB5R3	ENST00000686129.1	c.-48-12769delC	intron	N/A	ENSP00000508623.1	A0A8I5KVD2
CYB5R3	ENST00000693716.1	n.250-12769delC	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.138

AC:

20916

AN:

151970

Hom.:

2032

Cov.:

show subpopulations

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:

AN:

280

Hom.:

Cov.:

AF XY:

0.140

AC XY:

AN XY:

186

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AF:

0.0833

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.500

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AF:

0.250

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.136

AC:

AN:

236

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.550

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.138

AC:

20933

AN:

152086

Hom.:

2030

Cov.:

AF XY:

0.143

AC XY:

10629

AN XY:

74328

show subpopulations

African (AFR)

AF:

0.143

AC:

5936

AN:

41512

American (AMR)

AF:

0.111

AC:

1701

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.0813

AC:

282

AN:

3468

East Asian (EAS)

AF:

0.579

AC:

2954

AN:

5102

South Asian (SAS)

AF:

0.228

AC:

1097

AN:

4820

European-Finnish (FIN)

AF:

0.151

AC:

1603

AN:

10582

Middle Eastern (MID)

AF:

0.126

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.102

AC:

6935

AN:

67986

Other (OTH)

AF:

0.141

AC:

298

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

789

1578

2368

3157

3946

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

238

476

714

952

1190

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.130

Hom.:

169

Bravo

AF:

0.134

Asia WGS

AF:

0.345

AC:

1198

AN:

3476

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

-2.4

Splicing

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over