Variant rs5996200 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_000398.7(CYB5R3):c.132G>A(p.Pro44=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.134 in 1,612,544 control chromosomes in the GnomAD database, including 15,689 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.12 ( 1310 hom., cov: 32)

Exomes 𝑓: 0.14 ( 14379 hom. )

Consequence

CYB5R3
NM_000398.7 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.96

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 -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.33).

BP6

Variant 22-42636736-C-T is Benign according to our data. Variant chr22-42636736-C-T is described in ClinVar as [Benign]. Clinvar id is 256011.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.96 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.15 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYB5R3	NM_000398.7 linkuse as main transcript	c.132G>A	p.Pro44=	synonymous_variant	2/9	ENST00000352397.10	NP_000389.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYB5R3	ENST00000352397.10 linkuse as main transcript	c.132G>A	p.Pro44=	synonymous_variant	2/9	1	NM_000398.7	ENSP00000338461	P3	P00387-1

Frequencies

GnomAD3 genomes

AF:

0.125

AC:

18993

AN:

152146

Hom.:

1305

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0986

Gnomad AMI

AF:

0.243

Gnomad AMR

AF:

0.118

Gnomad ASJ

AF:

0.171

Gnomad EAS

AF:

0.00173

Gnomad SAS

AF:

0.0366

Gnomad FIN

AF:

0.131

Gnomad MID

AF:

0.196

Gnomad NFE

AF:

0.152

Gnomad OTH

AF:

0.149

GnomAD3 exomes

AF:

0.113

AC:

28110

AN:

248000

Hom.:

1867

AF XY:

0.113

AC XY:

15174

AN XY:

134386

show subpopulations

Gnomad AFR exome

AF:

0.100

Gnomad AMR exome

AF:

0.0832

Gnomad ASJ exome

AF:

0.174

Gnomad EAS exome

AF:

0.000820

Gnomad SAS exome

AF:

0.0397

Gnomad FIN exome

AF:

0.139

Gnomad NFE exome

AF:

0.151

Gnomad OTH exome

AF:

0.139

GnomAD4 exome

AF:

0.135

AC:

197319

AN:

1460280

Hom.:

14379

Cov.:

AF XY:

0.133

AC XY:

96739

AN XY:

726368

show subpopulations

Gnomad4 AFR exome

AF:

0.0926

Gnomad4 AMR exome

AF:

0.0886

Gnomad4 ASJ exome

AF:

0.176

Gnomad4 EAS exome

AF:

0.000454

Gnomad4 SAS exome

AF:

0.0421

Gnomad4 FIN exome

AF:

0.138

Gnomad4 NFE exome

AF:

0.149

Gnomad4 OTH exome

AF:

0.134

GnomAD4 genome

AF:

0.125

AC:

19018

AN:

152264

Hom.:

1310

Cov.:

AF XY:

0.122

AC XY:

9059

AN XY:

74446

show subpopulations

Gnomad4 AFR

AF:

0.0988

Gnomad4 AMR

AF:

0.117

Gnomad4 ASJ

AF:

0.171

Gnomad4 EAS

AF:

0.00173

Gnomad4 SAS

AF:

0.0373

Gnomad4 FIN

AF:

0.131

Gnomad4 NFE

AF:

0.152

Gnomad4 OTH

AF:

0.151

Alfa

AF:

0.149

Hom.:

2063

Bravo

AF:

0.125

Asia WGS

AF:

0.0370

AC:

134

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	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Nov 30, 2023	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 10, 2018	- -

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

-0.33

CADD

Benign

2.7

DANN

Benign

0.92

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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