11-7665517-C-A

Variant names:

Variant summary

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

The NM_016229.5(CYB5R2):c.688G>T(p.Ala230Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,846 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A230T) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

CYB5R2
NM_016229.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.733

Publications

0 publications found

Variant links:

Genes affected

CYB5R2 (HGNC:24376): (cytochrome b5 reductase 2) The protein encoded by this gene belongs to the flavoprotein pyridine nucleotide cytochrome reductase family of proteins. Cytochrome b-type NAD(P)H oxidoreductases are implicated in many processes including cholesterol biosynthesis, fatty acid desaturation and elongation, and respiratory burst in neutrophils and macrophages. Cytochrome b5 reductases have soluble and membrane-bound forms that are the product of alternative splicing. In animal cells, the membrane-bound form binds to the endoplasmic reticulum, where it is a member of a fatty acid desaturation complex. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2014]

CYB5R2 links:

PPFIBP2 (HGNC:9250): (PPFIA binding protein 2) This gene encodes a member of the LAR protein-tyrosine phosphatase-interacting protein (liprin) family. The encoded protein is a beta liprin and plays a role in axon guidance and neuronal synapse development by recruiting LAR protein-tyrosine phosphatases to the plasma membrane. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Feb 2012]

PPFIBP2 links:

Genome browser will be placed here

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=0.12889767).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016229.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CYB5R2	NM_016229.5	MANE Select	c.688G>T	p.Ala230Ser	missense	Exon 9 of 9	NP_057313.2
CYB5R2	NM_001302826.2		c.688G>T	p.Ala230Ser	missense	Exon 9 of 9	NP_001289755.1	Q6BCY4-1
CYB5R2	NM_001302827.1		c.684G>T	p.Leu228Leu	synonymous	Exon 8 of 8	NP_001289756.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CYB5R2	ENST00000299498.11	TSL:1 MANE Select	c.688G>T	p.Ala230Ser	missense	Exon 9 of 9	ENSP00000299498.6	Q6BCY4-1
CYB5R2	ENST00000524790.5	TSL:1	c.*87G>T		3_prime_UTR	Exon 10 of 10	ENSP00000435916.1	Q6BCY4-2
CYB5R2	ENST00000917897.1		c.754G>T	p.Ala252Ser	missense	Exon 9 of 9	ENSP00000587956.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1459846

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726232

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

33414

American (AMR)

AF:

0.00

AC:

AN:

44440

Ashkenazi Jewish (ASJ)

AF:

0.0000385

AC:

AN:

25948

East Asian (EAS)

AF:

0.00

AC:

AN:

39688

South Asian (SAS)

AF:

0.00

AC:

AN:

85880

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53358

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5704

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111102

Other (OTH)

AF:

0.00

AC:

AN:

60312

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.225

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.0057

BayesDel_noAF

Benign

-0.25

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.067

Eigen

Benign

-0.46

Eigen_PC

Benign

-0.52

FATHMM_MKL

Benign

0.22

LIST_S2

Uncertain

0.90

M_CAP

Benign

0.078

MetaRNN

Benign

0.13

MetaSVM

Uncertain

-0.11

PhyloP100

0.73

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.54

REVEL

Benign

0.27

Sift

Benign

0.063

Sift4G

Benign

0.52

Polyphen

0.13

Vest4

0.13

MutPred

0.38

Gain of disorder (P = 0.0518)

MVP

0.70

MPC

0.0074

ClinPred

0.87

GERP RS

3.9

Varity_R

0.21

gMVP

0.59

Mutation Taster

=90/10

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