19-52913715-G-A

Variant names:

• chr19-52913715-G-A
• rs8112177
• NM_001393938.1:c.142+1481C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001393938.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF888	NM_001393938.1	MANE Select	c.142+1481C>T		intron	N/A	NP_001380867.1
	ZNF888	NM_001384652.1		c.199+1481C>T		intron	N/A	NP_001371581.1
	ZNF888	NM_001310127.2		c.142+1481C>T		intron	N/A	NP_001297056.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF888	ENST00000638862.2	TSL:5 MANE Select	c.142+1481C>T		intron	N/A	ENSP00000491567.1
	ZNF888	ENST00000596623.2	TSL:5	n.551+1481C>T		intron	N/A

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

African (AFR) AF: 0.543 AC: 8393 AN: 15446

American (AMR) AF: 0.571 AC: 555 AN: 972

Ashkenazi Jewish (ASJ) AF: 0.373 AC: 1910 AN: 5116

East Asian (EAS) AF: 0.404 AC: 1461 AN: 3612

South Asian (SAS) AF: 0.467 AC: 7622 AN: 16312

European-Finnish (FIN) AF: 0.430 AC: 116 AN: 270

Middle Eastern (MID) AF: 0.255 AC: 411 AN: 1610

European-Non Finnish (NFE) AF: 0.346 AC: 261749 AN: 756990

Other (OTH) AF: 0.369 AC: 9995 AN: 27112

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

African (AFR) AF: 0.539 AC: 22337 AN: 41450

American (AMR) AF: 0.512 AC: 7825 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.373 AC: 1296 AN: 3472

East Asian (EAS) AF: 0.413 AC: 2136 AN: 5178

South Asian (SAS) AF: 0.470 AC: 2268 AN: 4826

European-Finnish (FIN) AF: 0.420 AC: 4434 AN: 10568

Middle Eastern (MID) AF: 0.276 AC: 81 AN: 294

European-Non Finnish (NFE) AF: 0.349 AC: 23735 AN: 67946

Other (OTH) AF: 0.409 AC: 866 AN: 2116

Alfa AF: 0.390 Hom.: 4000

Bravo AF: 0.436

Asia WGS AF: 0.508 AC: 1766 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.3
DANN	Benign	0.43
PhyloP100		-0.97

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

Other links and lift over

dbSNP: rs8112177; hg19: chr19-53416968;