11-7665448-G-A

Variant names:

• chr11-7665448-G-A
• rs373511090
• NM_016229.5:c.757C>T

Variant summary

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

The NM_016229.5(CYB5R2):​c.757C>T​(p.Pro253Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000124 in 1,613,604 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. P253A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000079 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000055 (0 hom.)
• Consequence: CYB5R2 NM_016229.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.53
• Publications: 0 publications found

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]

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]

ACMG classification

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

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYB5R2	NM_016229.5	MANE Select	c.757C>T	p.Pro253Ser	missense	Exon 9 of 9	NP_057313.2
	CYB5R2	NM_001302826.2		c.757C>T	p.Pro253Ser	missense	Exon 9 of 9	NP_001289755.1	Q6BCY4-1
	CYB5R2	NM_001302827.1		c.*60C>T		3_prime_UTR	Exon 8 of 8	NP_001289756.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYB5R2	ENST00000299498.11	TSL:1 MANE Select	c.757C>T	p.Pro253Ser	missense	Exon 9 of 9	ENSP00000299498.6	Q6BCY4-1
	CYB5R2	ENST00000524790.5	TSL:1	c.*156C>T		3_prime_UTR	Exon 10 of 10	ENSP00000435916.1	Q6BCY4-2
	CYB5R2	ENST00000917897.1		c.823C>T	p.Pro275Ser	missense	Exon 9 of 9	ENSP00000587956.1

Frequencies

GnomAD3 genomes AF: 0.0000788 AC: 12 AN: 152196 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000785

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000400 AC: 10 AN: 249892 AF XY: 0.0000370

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000290

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000547 AC: 8 AN: 1461408 Hom.: 0 Cov.: 38 AF XY: 0.00000413 AC XY: 3 AN XY: 726970

African (AFR) AF: 0.00 AC: 0 AN: 33462

American (AMR) AF: 0.000179 AC: 8 AN: 44648

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26106

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.00 AC: 0 AN: 86106

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53390

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111860

Other (OTH) AF: 0.00 AC: 0 AN: 60374

GnomAD4 genome AF: 0.0000788 AC: 12 AN: 152196 Hom.: 0 Cov.: 33 AF XY: 0.0000672 AC XY: 5 AN XY: 74358

African (AFR) AF: 0.00 AC: 0 AN: 41438

American (AMR) AF: 0.000785 AC: 12 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68042

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.12
CADD	Benign	16
DANN	Uncertain	1.0
DEOGEN2	Benign	0.30	T
Eigen	Benign	0.020
Eigen_PC	Benign	-0.16
FATHMM_MKL	Benign	0.65	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Uncertain	0.10	D
MetaRNN	Uncertain	0.63	D
MetaSVM	Uncertain	0.26	D
MutationAssessor	Pathogenic	2.9	M
PhyloP100		1.5
PrimateAI	Benign	0.31	T
PROVEAN	Pathogenic	-7.2	D
REVEL	Uncertain	0.35
Sift	Uncertain	0.016	D
Sift4G	Uncertain	0.010	D
Polyphen		0.77	P
Vest4		0.51
MutPred		0.61		Gain of catalytic residue at P253 (P = 0.0362)
MVP		0.90
MPC		0.0078
ClinPred		0.45	T
GERP RS		0.60
Varity_R		0.54
gMVP		0.80
Mutation Taster		=95/5	polymorphism

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

Other links and lift over

dbSNP: rs373511090; hg19: chr11-7686679;