22-22490916-C-T

Variant names:

• chr22-22490916-C-T
• rs5751168
• NM_080764.4:c.-68-1450G>A

Variant summary

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

The NM_080764.4(ZNF280B):​c.-68-1450G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.118 in 151,638 control chromosomes in the GnomAD database, including 1,240 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 0.12 (1240 hom., cov: 31)
• Consequence: ZNF280B NM_080764.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.216

Genes affected

ZNF280B (HGNC:23022): (zinc finger protein 280B) The protein encoded by this gene is a transcription factor that upregulates expression of MDM2, which negatively regulates p53 expression. This gene is highly expressed in prostate cancer cells, which leads to a reduction in p53 levels and an increase in growth of the cancer cells. Several transcript variants have been found for this gene, but only one of them is protein-coding. [provided by RefSeq, Jan 2015]

IGL (HGNC:5853):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.254 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF280B	NM_080764.4	c.-68-1450G>A		intron_variant	Intron 3 of 3	ENST00000626650.3	NP_542942.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF280B	ENST00000626650.3	c.-68-1450G>A		intron_variant	Intron 3 of 3	2	NM_080764.4	ENSP00000485750.1
ZNF280B	ENST00000619852.2	n.-68-1450G>A		intron_variant	Intron 3 of 4	1		ENSP00000480958.1

Frequencies

GnomAD3 genomes AF: 0.118 AC: 17831 AN: 151520 Hom.: 1242 Cov.: 31

Gnomad AFR AF: 0.134

Gnomad AMI AF: 0.0669

Gnomad AMR AF: 0.104

Gnomad ASJ AF: 0.155

Gnomad EAS AF: 0.220

Gnomad SAS AF: 0.265

Gnomad FIN AF: 0.129

Gnomad MID AF: 0.137

Gnomad NFE AF: 0.0898

Gnomad OTH AF: 0.116

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

GnomAD4 genome AF: 0.118 AC: 17828 AN: 151638 Hom.: 1240 Cov.: 31 AF XY: 0.121 AC XY: 8987 AN XY: 74060

Gnomad4 AFR AF: 0.134

Gnomad4 AMR AF: 0.104

Gnomad4 ASJ AF: 0.155

Gnomad4 EAS AF: 0.219

Gnomad4 SAS AF: 0.266

Gnomad4 FIN AF: 0.129

Gnomad4 NFE AF: 0.0898

Gnomad4 OTH AF: 0.114

Alfa AF: 0.101 Hom.: 1271

Bravo AF: 0.117

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	9.2

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs5751168; hg19: chr22-22845240;