ENST00000652335.1:c.-17-1503C>A

Variant names:

• chr16-151390-C-A
• rs6600143
• ENST00000652335.1:c.-17-1503C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000652335.1(HBZ):​c.-17-1503C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.785 in 152,200 control chromosomes in the GnomAD database, including 47,752 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 0.78 (47752 hom., cov: 33)
• Consequence: HBZ ENST00000652335.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.07
• Publications: 20 publications found

Genes affected

HBZ (HGNC:4835): (hemoglobin subunit zeta) Zeta-globin is an alpha-like hemoglobin. The zeta-globin polypeptide is synthesized in the yolk sac of the early embryo, while alpha-globin is produced throughout fetal and adult life. The zeta-globin gene is a member of the human alpha-globin gene cluster that includes five functional genes and two pseudogenes. The order of genes is: 5' - zeta - pseudozeta - mu - pseudoalpha-1 - alpha-2 -alpha-1 - theta1 - 3'. [provided by RefSeq, Nov 2009]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.938 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HBZ	ENST00000652335.1	c.-17-1503C>A		intron_variant	Intron 1 of 2			ENSP00000498371.1

Frequencies

GnomAD3 genomes AF: 0.784 AC: 119302 AN: 152082 Hom.: 47677 Cov.: 33

Gnomad AFR AF: 0.945

Gnomad AMI AF: 0.818

Gnomad AMR AF: 0.799

Gnomad ASJ AF: 0.791

Gnomad EAS AF: 0.725

Gnomad SAS AF: 0.778

Gnomad FIN AF: 0.680

Gnomad MID AF: 0.826

Gnomad NFE AF: 0.704

Gnomad OTH AF: 0.769

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

GnomAD4 genome AF: 0.785 AC: 119436 AN: 152200 Hom.: 47752 Cov.: 33 AF XY: 0.784 AC XY: 58294 AN XY: 74396

African (AFR) AF: 0.946 AC: 39292 AN: 41556

American (AMR) AF: 0.800 AC: 12228 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.791 AC: 2746 AN: 3472

East Asian (EAS) AF: 0.725 AC: 3755 AN: 5180

South Asian (SAS) AF: 0.778 AC: 3752 AN: 4822

European-Finnish (FIN) AF: 0.680 AC: 7194 AN: 10576

Middle Eastern (MID) AF: 0.830 AC: 244 AN: 294

European-Non Finnish (NFE) AF: 0.704 AC: 47845 AN: 67982

Other (OTH) AF: 0.773 AC: 1634 AN: 2114

Alfa AF: 0.744 Hom.: 109661

Bravo AF: 0.800

Asia WGS AF: 0.792 AC: 2752 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.30
DANN	Benign	0.37
PhyloP100		-1.1

Splicing

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

Other links and lift over

dbSNP: rs6600143; hg19: chr16-201389;