rs12149862

Variant names:

• chr16-69463300-G-A
• rs12149862
• NM_030579.3:c.*780G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 18 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
CYB5B	NM_030579.3	c.*780G>A		3_prime_UTR_variant	Exon 5 of 5	ENST00000307892.13	NP_085056.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYB5B	ENST00000307892.13	c.*780G>A		3_prime_UTR_variant	Exon 5 of 5	1	NM_030579.3	ENSP00000308430.8

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.00 AC: 0 AN: 2

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.167 AC: 3 AN: 18

Other (OTH) AF: 0.00 AC: 0 AN: 2

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

African (AFR) AF: 0.159 AC: 6592 AN: 41380

American (AMR) AF: 0.138 AC: 2102 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.303 AC: 1050 AN: 3466

East Asian (EAS) AF: 0.00754 AC: 39 AN: 5174

South Asian (SAS) AF: 0.184 AC: 883 AN: 4790

European-Finnish (FIN) AF: 0.164 AC: 1721 AN: 10506

Middle Eastern (MID) AF: 0.248 AC: 73 AN: 294

European-Non Finnish (NFE) AF: 0.186 AC: 12657 AN: 67954

Other (OTH) AF: 0.191 AC: 402 AN: 2104

Alfa AF: 0.174 Hom.: 594

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
PhyloP100		0.29
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=100/0	polymorphism (auto)

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: rs12149862; hg19: chr16-69497203;