Genetic Variant CYB5R4:p.Ile190Val (chr6-83921085-A-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_016230.4(CYB5R4):c.568A>G(p.Ile190Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CYB5R4
NM_016230.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.93

Publications

0 publications found

Variant links:

Genes affected

CYB5R4 (HGNC:20147): (cytochrome b5 reductase 4) NCB5OR is a flavohemoprotein that contains functional domains found in both cytochrome b5 (CYB5A; MIM 613218) and CYB5 reductase (CYB5R3; MIM 613213) (Zhu et al., 1999 [PubMed 10611283]).[supplied by OMIM, Jan 2010]

CYB5R4 links:

RIPPLY2-CYB5R4 (HGNC:):

RIPPLY2-CYB5R4 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.12766173).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016230.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CYB5R4	NM_016230.4	MANE Select	c.568A>G	p.Ile190Val	missense	Exon 8 of 16	NP_057314.2	Q7L1T6
RIPPLY2-CYB5R4	NM_001400774.1		c.466A>G	p.Ile156Val	missense	Exon 9 of 17	NP_001387703.1	B2R7W7
RIPPLY2-CYB5R4	NR_174603.1		n.727A>G		non_coding_transcript_exon	Exon 9 of 18

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CYB5R4	ENST00000369681.10	TSL:1 MANE Select	c.568A>G	p.Ile190Val	missense	Exon 8 of 16	ENSP00000358695.3	Q7L1T6
CYB5R4	ENST00000942770.1		c.586A>G	p.Ile196Val	missense	Exon 8 of 16	ENSP00000612829.1
CYB5R4	ENST00000942768.1		c.568A>G	p.Ile190Val	missense	Exon 8 of 16	ENSP00000612827.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1343178

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

666820

African (AFR)

AF:

0.00

AC:

AN:

28346

American (AMR)

AF:

0.00

AC:

AN:

27978

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22780

East Asian (EAS)

AF:

0.00

AC:

AN:

36062

South Asian (SAS)

AF:

0.00

AC:

AN:

74796

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50320

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5206

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1042498

Other (OTH)

AF:

0.00

AC:

AN:

55192

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.073

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.63

CADD

Benign

(source)

DANN

Benign

0.87

DEOGEN2

Benign

0.028

Eigen

Benign

-0.44

Eigen_PC

Benign

-0.25

FATHMM_MKL

Benign

0.61

LIST_S2

Benign

0.69

M_CAP

Benign

0.0036

MetaRNN

Benign

0.13

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.3

PhyloP100

1.9

PrimateAI

Benign

0.35

PROVEAN

Benign

-0.10

REVEL

Benign

0.032

Sift

Benign

0.26

Sift4G

Benign

0.50

Polyphen

0.0

Vest4

0.27

MutPred

0.56

Gain of catalytic residue at I190 (P = 0.0592)

MVP

0.35

MPC

0.12

ClinPred

0.29

GERP RS

2.3

Varity_R

0.040

gMVP

0.22

Mutation Taster

=97/3

polymorphism

(source)

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

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over