rs11595684

Positions:

• chr10-37794876-T-C

Variant summary

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

The NR_051997.1(ZNF33BP1):​n.300A>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.109 in 154,572 control chromosomes in the GnomAD database, including 1,174 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 0.11 (1161 hom., cov: 33)
  • Exomes 𝑓: 0.10 (13 hom.)
• Consequence: ZNF33BP1 NR_051997.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.72

Genes affected

ZNF33BP1 (HGNC:44975): (zinc finger protein 33B pseudogene 1)

ZNF248 (HGNC:13041): (zinc finger protein 248) Predicted to enable DNA-binding transcription repressor activity, RNA polymerase II-specific and RNA polymerase II transcription regulatory region sequence-specific DNA binding activity. Predicted to be involved in negative regulation of transcription by RNA polymerase II. Predicted to be located 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=-0.86).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.182 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF33BP1	NR_051997.1	n.300A>G		non_coding_transcript_exon_variant	1/1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF33BP1	ENST00000452497.1	n.1234A>G		non_coding_transcript_exon_variant	1/1
ZNF248	ENST00000615949.6	c.331-18301A>G		intron_variant		5		ENSP00000477940

Frequencies

GnomAD3 genomes AF: 0.110 AC: 16672 AN: 152150 Hom.: 1160 Cov.: 33

Gnomad AFR AF: 0.0381

Gnomad AMI AF: 0.125

Gnomad AMR AF: 0.187

Gnomad ASJ AF: 0.139

Gnomad EAS AF: 0.105

Gnomad SAS AF: 0.0635

Gnomad FIN AF: 0.0930

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.139

Gnomad OTH AF: 0.133

GnomAD4 exome AF: 0.101 AC: 232 AN: 2304 Hom.: 13 Cov.: 0 AF XY: 0.0953 AC XY: 117 AN XY: 1228

Gnomad4 AFR exome AF: 0.100

Gnomad4 AMR exome AF: 0.250

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.125

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0935

Gnomad4 NFE exome AF: 0.131

Gnomad4 OTH exome AF: 0.0862

GnomAD4 genome AF: 0.110 AC: 16674 AN: 152268 Hom.: 1161 Cov.: 33 AF XY: 0.110 AC XY: 8183 AN XY: 74458

Gnomad4 AFR AF: 0.0382

Gnomad4 AMR AF: 0.187

Gnomad4 ASJ AF: 0.139

Gnomad4 EAS AF: 0.105

Gnomad4 SAS AF: 0.0631

Gnomad4 FIN AF: 0.0930

Gnomad4 NFE AF: 0.139

Gnomad4 OTH AF: 0.132

Alfa AF: 0.121 Hom.: 145

Bravo AF: 0.118

Asia WGS AF: 0.0830 AC: 287 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	4.1
DANN	Benign	0.71

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11595684; hg19: chr10-38083804;