rs361901

Positions:

• chr22-22507676-A-G

Variant summary

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

The NM_080764.4(ZNF280B):​c.-187+134T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.149 in 151,660 control chromosomes in the GnomAD database, including 1,959 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 0.15 (1959 hom., cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ZNF280B NM_080764.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.07

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (Cadd=0.977).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.282 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF280B	NM_080764.4	c.-187+134T>C		intron_variant		ENST00000626650.3	NP_542942.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF280B	ENST00000626650.3	c.-187+134T>C		intron_variant		2	NM_080764.4	ENSP00000485750	P1
ZNF280B	ENST00000619852.2	c.-187+134T>C		intron_variant, NMD_transcript_variant		1		ENSP00000480958

Frequencies

GnomAD3 genomes AF: 0.149 AC: 22523 AN: 151540 Hom.: 1959 Cov.: 31

Gnomad AFR AF: 0.209

Gnomad AMI AF: 0.0680

Gnomad AMR AF: 0.120

Gnomad ASJ AF: 0.164

Gnomad EAS AF: 0.220

Gnomad SAS AF: 0.294

Gnomad FIN AF: 0.146

Gnomad MID AF: 0.150

Gnomad NFE AF: 0.104

Gnomad OTH AF: 0.140

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 6 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 4

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.149 AC: 22526 AN: 151660 Hom.: 1959 Cov.: 31 AF XY: 0.152 AC XY: 11284 AN XY: 74090

Gnomad4 AFR AF: 0.209

Gnomad4 AMR AF: 0.120

Gnomad4 ASJ AF: 0.164

Gnomad4 EAS AF: 0.219

Gnomad4 SAS AF: 0.295

Gnomad4 FIN AF: 0.146

Gnomad4 NFE AF: 0.104

Gnomad4 OTH AF: 0.138

Alfa AF: 0.116 Hom.: 1909

Bravo AF: 0.150

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
CADD	Benign	0.98

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs361901; hg19: -;