rs7251313

Positions:

• chr19-52921071-G-A
• chr19-52921071-G-C

Variant summary

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

The NM_001393938.1(ZNF888):​c.-177-2134C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.438 in 151,956 control chromosomes in the GnomAD database, including 15,845 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 0.44 (15845 hom., cov: 32)
• Consequence: ZNF888 NM_001393938.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.533

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=-0.96).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.539 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF888	NM_001393938.1	c.-177-2134C>T		intron_variant		ENST00000638862.2	NP_001380867.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF888	ENST00000638862.2	c.-177-2134C>T		intron_variant		5	NM_001393938.1	ENSP00000491567	P1
ZNF888	ENST00000596623.2	n.102+2298C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.439 AC: 66603 AN: 151836 Hom.: 15851 Cov.: 32

Gnomad AFR AF: 0.273

Gnomad AMI AF: 0.469

Gnomad AMR AF: 0.379

Gnomad ASJ AF: 0.506

Gnomad EAS AF: 0.267

Gnomad SAS AF: 0.458

Gnomad FIN AF: 0.542

Gnomad MID AF: 0.506

Gnomad NFE AF: 0.544

Gnomad OTH AF: 0.441

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.438 AC: 66596 AN: 151956 Hom.: 15845 Cov.: 32 AF XY: 0.434 AC XY: 32238 AN XY: 74258

Gnomad4 AFR AF: 0.273

Gnomad4 AMR AF: 0.379

Gnomad4 ASJ AF: 0.506

Gnomad4 EAS AF: 0.267

Gnomad4 SAS AF: 0.458

Gnomad4 FIN AF: 0.542

Gnomad4 NFE AF: 0.544

Gnomad4 OTH AF: 0.435

Alfa AF: 0.520 Hom.: 32339

Bravo AF: 0.419

Asia WGS AF: 0.333 AC: 1161 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.0
DANN	Benign	0.71

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: rs7251313; hg19: chr19-53424324;