rs10512421

chr17-18663351-G-Achr17-18663351-G-C

Variant summary

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

The NR_160540.1(ZNF286B):n.433-124C>T variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0145 in 1,497,356 control chromosomes in the GnomAD database, including 2,252 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 0.071 (1266 hom., cov: 32)
  • Exomes 𝑓: 0.0081 (986 hom.)
• Consequence: ZNF286B NR_160540.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.533

Genes affected

ZNF286B (HGNC:33241): (zinc finger protein 286B (pseudogene)) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [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=-0.79).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.238 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF286B	NR_160540.1	n.433-124C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF286B	ENST00000668878.2	n.322-124C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0707 AC: 10748 AN: 152054 Hom.: 1263 Cov.: 32

Gnomad AFR AF: 0.242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0275

Gnomad ASJ AF: 0.0231

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00166

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.00173

Gnomad OTH AF: 0.0522

GnomAD4 exome AF: 0.00812 AC: 10921 AN: 1345184 Hom.: 986 AF XY: 0.00733 AC XY: 4835 AN XY: 659558

Gnomad4 AFR exome AF: 0.248

Gnomad4 AMR exome AF: 0.0180

Gnomad4 ASJ exome AF: 0.0207

Gnomad4 EAS exome AF: 0.000113

Gnomad4 SAS exome AF: 0.000800

Gnomad4 FIN exome AF: 0.0000240

Gnomad4 NFE exome AF: 0.00105

Gnomad4 OTH exome AF: 0.0217

GnomAD4 genome AF: 0.0708 AC: 10770 AN: 152172 Hom.: 1266 Cov.: 32 AF XY: 0.0691 AC XY: 5143 AN XY: 74414

Gnomad4 AFR AF: 0.242

Gnomad4 AMR AF: 0.0274

Gnomad4 ASJ AF: 0.0231

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00104

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00174

Gnomad4 OTH AF: 0.0516

Alfa AF: 0.00658 Hom.: 100

Bravo AF: 0.0796

Asia WGS AF: 0.0180 AC: 64 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
Cadd	Benign	8.4
Dann	Benign	0.43

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs10512421; hg19: chr17-18566664;