16-69421625-G-A

Variant names:

• chr16-69421625-G-A
• rs728546
• ENST00000686649.1:c.-94+23159G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 11 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=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.766 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000686649.1. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYB5B	ENST00000686649.1		c.-94+23159G>A		intron	N/A	ENSP00000509909.1

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

African (AFR) AF: 0.660 AC: 27358 AN: 41462

American (AMR) AF: 0.714 AC: 10913 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.755 AC: 2619 AN: 3468

East Asian (EAS) AF: 0.411 AC: 2121 AN: 5164

South Asian (SAS) AF: 0.624 AC: 3004 AN: 4814

European-Finnish (FIN) AF: 0.689 AC: 7270 AN: 10550

Middle Eastern (MID) AF: 0.810 AC: 238 AN: 294

European-Non Finnish (NFE) AF: 0.771 AC: 52452 AN: 68004

Other (OTH) AF: 0.741 AC: 1563 AN: 2110

Alfa AF: 0.753 Hom.: 120743

Bravo AF: 0.712

Asia WGS AF: 0.537 AC: 1868 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	2.1
DANN	Benign	0.63
PhyloP100		-0.23

Splicing

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

Other links and lift over

dbSNP: rs728546; hg19: chr16-69455528;