1-202966580-C-A

Variant names:

• chr1-202966580-C-A
• rs772003868
• NM_016243.3:c.186G>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_016243.3(CYB5R1):​c.186G>T​(p.Lys62Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,892 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CYB5R1 NM_016243.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.622
• Publications: 0 publications found

Genes affected

CYB5R1 (HGNC:13397): (cytochrome b5 reductase 1) Predicted to enable FAD binding activity. Predicted to be involved in bicarbonate transport. Located in extracellular exosome; membrane; and mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016243.3. 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
	CYB5R1	NM_016243.3	MANE Select	c.186G>T	p.Lys62Asn	missense	Exon 3 of 9	NP_057327.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYB5R1	ENST00000367249.9	TSL:1 MANE Select	c.186G>T	p.Lys62Asn	missense	Exon 3 of 9	ENSP00000356218.4	Q9UHQ9
	CYB5R1	ENST00000893436.1		c.186G>T	p.Lys62Asn	missense	Exon 3 of 9	ENSP00000563495.1
	CYB5R1	ENST00000964627.1		c.186G>T	p.Lys62Asn	missense	Exon 3 of 9	ENSP00000634686.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461892 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727248

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

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

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1112010

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.76
BayesDel_addAF	Benign	-0.0042	T
BayesDel_noAF	Benign	-0.24
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.35	T
Eigen	Uncertain	0.25
Eigen_PC	Uncertain	0.35
FATHMM_MKL	Benign	0.74	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.034	D
MetaRNN	Uncertain	0.43	T
MetaSVM	Uncertain	0.29	D
MutationAssessor	Uncertain	2.3	M
PhyloP100		0.62
PrimateAI	Benign	0.44	T
PROVEAN	Uncertain	-2.4	N
REVEL	Uncertain	0.43
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.050	T
Polyphen		0.14	B
Vest4		0.48
MutPred		0.68		Loss of MoRF binding (P = 0.0356)
MVP		0.93
MPC		0.24
ClinPred		0.99	D
GERP RS		5.0
PromoterAI		0.032	Neutral
Varity_R		0.59
gMVP		0.84
Mutation Taster		=77/23	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.49		Details are displayed if max score is > 0.2
DS_AL_spliceai		0.49		Position offset: 20

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs772003868; hg19: chr1-202935708;