rs12149862

Positions:

• chr16-69463300-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_030579.3(CYB5B):​c.*780G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.169 in 151,866 control chromosomes in the GnomAD database, including 2,307 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.17 (2307 hom., cov: 31)
  • Exomes 𝑓: 0.13 (0 hom.)
• Consequence: CYB5B NM_030579.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.286

Genes affected

CYB5B (HGNC:24374): (cytochrome b5 type B) Enables heme binding activity. Contributes to nitrite reductase (NO-forming) activity. Involved in nitric oxide biosynthetic process. Located in membrane. Part of nitric-oxide synthase complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.184 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYB5B	NM_030579.3	c.*780G>A		3_prime_UTR_variant	5/5	ENST00000307892.13	NP_085056.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYB5B	ENST00000307892.13	c.*780G>A		3_prime_UTR_variant	5/5	1	NM_030579.3	ENSP00000308430	P2

Frequencies

GnomAD3 genomes AF: 0.169 AC: 25644 AN: 151722 Hom.: 2306 Cov.: 31

Gnomad AFR AF: 0.159

Gnomad AMI AF: 0.166

Gnomad AMR AF: 0.138

Gnomad ASJ AF: 0.303

Gnomad EAS AF: 0.00752

Gnomad SAS AF: 0.185

Gnomad FIN AF: 0.164

Gnomad MID AF: 0.248

Gnomad NFE AF: 0.186

Gnomad OTH AF: 0.193

GnomAD4 exome AF: 0.125 AC: 3 AN: 24 Hom.: 0 Cov.: 0 AF XY: 0.0714 AC XY: 1 AN XY: 14

Gnomad4 EAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.167

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.169 AC: 25670 AN: 151842 Hom.: 2307 Cov.: 31 AF XY: 0.166 AC XY: 12344 AN XY: 74186

Gnomad4 AFR AF: 0.159

Gnomad4 AMR AF: 0.138

Gnomad4 ASJ AF: 0.303

Gnomad4 EAS AF: 0.00754

Gnomad4 SAS AF: 0.184

Gnomad4 FIN AF: 0.164

Gnomad4 NFE AF: 0.186

Gnomad4 OTH AF: 0.191

Alfa AF: 0.174 Hom.: 584

Bravo AF: 0.164

Asia WGS AF: 0.139 AC: 484 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	12
DANN	Benign	0.85
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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

LitVar

Other links and lift over

dbSNP: rs12149862; hg19: chr16-69497203;