rs728546

chr16-69421625-G-A

Variant summary

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

The ENST00000686649.1(CYB5B):c.-94+23159G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.711 in 152,056 control chromosomes in the GnomAD database, including 38,875 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 0.71 (38875 hom., cov: 32)
• Consequence: CYB5B ENST00000686649.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.231

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=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.766 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYB5B	ENST00000686649.1	c.-94+23159G>A		intron_variant

Frequencies

GnomAD3 genomes AF: 0.711 AC: 108074 AN: 151938 Hom.: 38858 Cov.: 32

Gnomad AFR AF: 0.660

Gnomad AMI AF: 0.656

Gnomad AMR AF: 0.715

Gnomad ASJ AF: 0.755

Gnomad EAS AF: 0.411

Gnomad SAS AF: 0.624

Gnomad FIN AF: 0.689

Gnomad MID AF: 0.816

Gnomad NFE AF: 0.771

Gnomad OTH AF: 0.747

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.711 AC: 108135 AN: 152056 Hom.: 38875 Cov.: 32 AF XY: 0.705 AC XY: 52402 AN XY: 74314

Gnomad4 AFR AF: 0.660

Gnomad4 AMR AF: 0.714

Gnomad4 ASJ AF: 0.755

Gnomad4 EAS AF: 0.411

Gnomad4 SAS AF: 0.624

Gnomad4 FIN AF: 0.689

Gnomad4 NFE AF: 0.771

Gnomad4 OTH AF: 0.741

Alfa AF: 0.762 Hom.: 74482

Bravo AF: 0.712

Asia WGS AF: 0.537 AC: 1868 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
Cadd	Benign	2.1
Dann	Benign	0.63

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs728546; hg19: chr16-69455528;