rs8112177

Positions:

• chr19-52913715-G-A

Variant summary

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

The NM_001393938.1(ZNF888):​c.142+1481C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.365 in 979,474 control chromosomes in the GnomAD database, including 67,172 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 0.43 (14746 hom., cov: 33)
  • Exomes 𝑓: 0.35 (52426 hom.)
• Consequence: ZNF888 NM_001393938.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.973

Genes affected

ZNF888 (HGNC:38695): (zinc finger protein 888) 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=-1.04).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.533 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF888	NM_001393938.1	c.142+1481C>T		intron_variant		ENST00000638862.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF888	ENST00000638862.2	c.142+1481C>T		intron_variant		5	NM_001393938.1	P1
ZNF888	ENST00000596623.2	n.551+1481C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.429 AC: 65241 AN: 151916 Hom.: 14706 Cov.: 33

Gnomad AFR AF: 0.539

Gnomad AMI AF: 0.407

Gnomad AMR AF: 0.511

Gnomad ASJ AF: 0.373

Gnomad EAS AF: 0.412

Gnomad SAS AF: 0.469

Gnomad FIN AF: 0.420

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.349

Gnomad OTH AF: 0.402

GnomAD4 exome AF: 0.353 AC: 292212 AN: 827440 Hom.: 52426 Cov.: 23 AF XY: 0.353 AC XY: 135057 AN XY: 382202

Gnomad4 AFR exome AF: 0.543

Gnomad4 AMR exome AF: 0.571

Gnomad4 ASJ exome AF: 0.373

Gnomad4 EAS exome AF: 0.404

Gnomad4 SAS exome AF: 0.467

Gnomad4 FIN exome AF: 0.430

Gnomad4 NFE exome AF: 0.346

Gnomad4 OTH exome AF: 0.369

GnomAD4 genome AF: 0.430 AC: 65348 AN: 152034 Hom.: 14746 Cov.: 33 AF XY: 0.435 AC XY: 32293 AN XY: 74296

Gnomad4 AFR AF: 0.539

Gnomad4 AMR AF: 0.512

Gnomad4 ASJ AF: 0.373

Gnomad4 EAS AF: 0.413

Gnomad4 SAS AF: 0.470

Gnomad4 FIN AF: 0.420

Gnomad4 NFE AF: 0.349

Gnomad4 OTH AF: 0.409

Alfa AF: 0.391 Hom.: 2025

Bravo AF: 0.436

Asia WGS AF: 0.508 AC: 1766 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.3
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: rs8112177; hg19: chr19-53416968;