chr6-83909036-A-C

Variant names:

• chr6-83909036-A-C
• rs201467859
• NM_016230.4:c.358A>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_016230.4(CYB5R4):​c.358A>C​(p.Met120Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000547 in 1,461,646 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. M120V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000055 (0 hom.)
• Consequence: CYB5R4 NM_016230.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.17
• Publications: 0 publications found

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]

RIPPLY2-CYB5R4 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.40191776).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYB5R4	NM_016230.4	c.358A>C	p.Met120Leu	missense_variant	Exon 4 of 16	ENST00000369681.10	NP_057314.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYB5R4	ENST00000369681.10	c.358A>C	p.Met120Leu	missense_variant	Exon 4 of 16	1	NM_016230.4	ENSP00000358695.3
CYB5R4	ENST00000369679.4	c.256A>C	p.Met86Leu	missense_variant	Exon 4 of 5	3		ENSP00000358693.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000547 AC: 8 AN: 1461646 Hom.: 0 Cov.: 30 AF XY: 0.00000550 AC XY: 4 AN XY: 727108

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44688

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39684

South Asian (SAS) AF: 0.00 AC: 0 AN: 86238

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53406

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00000720 AC: 8 AN: 1111872

Other (OTH) AF: 0.00 AC: 0 AN: 60386

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.44
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.030
CADD	Uncertain	25
DANN	Uncertain	0.98
DEOGEN2	Benign	0.19	T;T
Eigen	Uncertain	0.19
Eigen_PC	Uncertain	0.34
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.93	D;D
M_CAP	Benign	0.065	D
MetaRNN	Benign	0.40	T;T
MetaSVM	Benign	-0.63	T
MutationAssessor	Benign	0.70	N;.
PhyloP100		5.2
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-1.2	N;N
REVEL	Uncertain	0.48
Sift	Pathogenic	0.0	D;T
Sift4G	Benign	0.091	T;T
Polyphen		0.56	P;.
Vest4		0.47
MutPred		0.70		Gain of helix (P = 0.062);.;
MVP		0.82
MPC		0.60
ClinPred		0.70	D
GERP RS		5.7
Varity_R		0.87
gMVP		0.82
Mutation Taster		=64/36	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: rs201467859; hg19: chr6-84618755;