Variant chr22-42636864-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000398.7(CYB5R3):c.22-18C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.117 in 1,611,294 control chromosomes in the GnomAD database, including 16,889 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.12 ( 1778 hom., cov: 32)

Exomes 𝑓: 0.12 ( 15111 hom. )

Consequence

CYB5R3
NM_000398.7 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.336

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 22-42636864-G-T is Benign according to our data. Variant chr22-42636864-G-T is described in ClinVar as [Benign]. Clinvar id is 256012.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.564 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CYB5R3	NM_000398.7 linkuse as main transcript	c.22-18C>A		intron_variant		ENST00000352397.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYB5R3	ENST00000352397.10 linkuse as main transcript	c.22-18C>A		intron_variant		1	NM_000398.7	P3	P00387-1

Frequencies

GnomAD3 genomes

AF:

0.123

AC:

18672

AN:

152102

Hom.:

1784

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0900

Gnomad AMI

AF:

0.0987

Gnomad AMR

AF:

0.104

Gnomad ASJ

AF:

0.0804

Gnomad EAS

AF:

0.582

Gnomad SAS

AF:

0.229

Gnomad FIN

AF:

0.153

Gnomad MID

AF:

0.117

Gnomad NFE

AF:

0.102

Gnomad OTH

AF:

0.133

GnomAD3 exomes

AF:

0.149

AC:

36798

AN:

246602

Hom.:

4803

AF XY:

0.151

AC XY:

20157

AN XY:

133548

show subpopulations

Gnomad AFR exome

AF:

0.0908

Gnomad AMR exome

AF:

0.0830

Gnomad ASJ exome

AF:

0.0784

Gnomad EAS exome

AF:

0.589

Gnomad SAS exome

AF:

0.188

Gnomad FIN exome

AF:

0.154

Gnomad NFE exome

AF:

0.103

Gnomad OTH exome

AF:

0.131

GnomAD4 exome

AF:

0.117

AC:

170561

AN:

1459074

Hom.:

15111

Cov.:

AF XY:

0.120

AC XY:

86846

AN XY:

725798

show subpopulations

Gnomad4 AFR exome

AF:

0.0925

Gnomad4 AMR exome

AF:

0.0851

Gnomad4 ASJ exome

AF:

0.0815

Gnomad4 EAS exome

AF:

0.564

Gnomad4 SAS exome

AF:

0.189

Gnomad4 FIN exome

AF:

0.156

Gnomad4 NFE exome

AF:

0.0955

Gnomad4 OTH exome

AF:

0.135

GnomAD4 genome

AF:

0.123

AC:

18680

AN:

152220

Hom.:

1778

Cov.:

AF XY:

0.129

AC XY:

9601

AN XY:

74418

show subpopulations

Gnomad4 AFR

AF:

0.0902

Gnomad4 AMR

AF:

0.104

Gnomad4 ASJ

AF:

0.0804

Gnomad4 EAS

AF:

0.581

Gnomad4 SAS

AF:

0.229

Gnomad4 FIN

AF:

0.153

Gnomad4 NFE

AF:

0.102

Gnomad4 OTH

AF:

0.132

Alfa

AF:

0.0968

Hom.:

458

Bravo

AF:

0.116

Asia WGS

AF:

0.345

AC:

1197

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Nov 29, 2023	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.085

DANN

Benign

0.69

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.3

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over